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25 results on '"Sayandip Mukherjee"'

1. Chemical inactivation of two non-enveloped viruses results in distinct thermal unfolding patterns and morphological alterations

Author: Pankhuri Narula, Milan Kumar Lokshman, Sandip B. Pathak, Sayandip Mukherjee, and Manidipa Banerjee
Subjects: Non-enveloped viruses, Human adenovirus, Feline calicivirus, Chemical inactivation, Calorimetry, Microbiology, QR1-502
Abstract: Abstract Background Non-enveloped viruses, which lack a lipid envelope, display higher resistance to disinfectants, soaps and sanitizers compared to enveloped viruses. The capsids of these viruses are highly stable and symmetric protein shells that resist inactivation by commonly employed virucidal agents. This group of viruses include highly transmissible human pathogens such as Rotavirus, Poliovirus, Foot and Mouth Disease Virus, Norovirus and Adenovirus; thus, devising appropriate strategies for chemical disinfection is essential. Results In this study, we tested a mild, hypoallergenic combination of a denaturant, alcohol, and organic acid (3.2% citric acid, 1% urea and 70% ethanol, pH4) on two representative non-enveloped viruses – Human Adenovirus 5 (HAdV5) and Feline Calicivirus (FCV)– and evaluated the pathways of capsid neutralization using biophysical methods. The conformational shifts in the capsid upon chemical treatment were studied using Differential Scanning Calorimetry (DSC), while the morphological alterations were visualized concurrently using Transmission Electron Microscopy (TEM). We found that while treatment of purified HAdV5 particles with a formulation resulted in thermal instability and, large scale aggregation; similar treatment of FCV particles resulted in complete collapse of the capsids. Further, while individual components of the formulation caused significant damage to the capsids, a synergistic action of the whole formulation was evident against both non-enveloped viruses tested. Conclusions The distinct effects of the chemical treatment on the morphology of HAdV5 and FCV suggests that non-enveloped viruses with icosahedral geometry can follow different morphological pathways to inactivation. Synergistic effect of whole formulation is more effective compared to individual components. Molecular level understanding of inactivation pathways may result in the design and development of effective mass-market formulations for rapid neutralization of non-enveloped viruses.
Published: 2024
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2. Development of a pseudo-typed virus particle based method to determine the efficacy of virucidal agents

Author: Jordan Thomas, Farah Mughal, Kelly J. Roper, Aurelia Kotsiri, Wejdan Albalawi, Abdullateef Alshehri, Yugandhar B. S. Reddy, Sayandip Mukherjee, Georgios Pollakis, William A. Paxton, and Michael Hoptroff
Subjects: Medicine, Science
Abstract: Abstract The ongoing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has highlighted the threat that viral outbreaks pose to global health. A key tool in the arsenal to prevent and control viral disease outbreaks is disinfection of equipment and surfaces with formulations that contain virucidal agents (VA). However, assessment of the efficacy of virus inactivation often requires live virus assays or surrogate viruses such as Modified Vaccinia Virus Ankara (MVA), which can be expensive, time consuming and technically challenging. Therefore, we have developed a pseudo-typed virus (PV) based approach to assess the inactivation of enveloped viruses with a fast and quantitative output that can be adapted to emerging viruses. Additionally, we have developed a method to completely remove the cytotoxicity of virucidal agents while retaining the required sensitivity to measure PV infectivity. Our results indicated that the removal of cytotoxicity was an essential step to accurately measure virus inactivation. Further, we demonstrated that there was no difference in susceptibility to virus inactivation between PVs that express the envelopes of HIV-1, SARS-CoV-2, and Influenza A/Indonesia. Therefore, we have developed an effective and safe alternative to live virus assays that enables the rapid assessment of virucidal activity for the development and optimization of virucidal reagents.
Published: 2024
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3. SG-APSIC1050: Personal care formulations prove effective against evolving variants of SARS-CoV-2: Implications for public health and hygiene

Author: Sayandip Mukherjee, Carol K Vincent, Harshinie W Jayasekera, and Ashish S Yekhe
Subjects: Infectious and parasitic diseases, RC109-216, Public aspects of medicine, RA1-1270
Abstract: Objectives: Early in the COVID-19 pandemic, global health authorities identified and emphasized the importance of practicing proper hand hygiene to reduce the transmission of SARS-CoV-2 and to diminish the chances of becoming infected. It is well established in the scientific literature that surfactants and alcohols are capable of inactivating enveloped viruses such as SARS-CoV-2. However, given the novel nature of the virus, Unilever adopted an evidence-based approach to demonstrate virucidal efficacy of marketed bar soaps, liquid handwashes, and alcohol-based hand sanitizers against the original and selected variants of SARS-CoV-2. Methods: High titers of clinically isolated and laboratory-propagated SARS-CoV-2 strains were subjected to a range of selected proprietary formulations from Unilever at end-user–relevant dilutions, temperature, and contact duration, and were tested according to the internationally recognized ASTM E-1052 test protocol. Results: All tested personal-care formulations were effective against the parental SARS-CoV-2 strain as well as the β (beta) and δ (delta) variants of concern. More specifically, bar soaps with a varying concentration of total fatty matter content and liquid handwashes with varying levels of total surfactants reduced the viral titer by >99.9% within 20 seconds. Alcohol-based hand sanitizers demonstrated >99.99% reduction of input viral load within 15 seconds of contact with the viral inoculum. Conclusions: In conclusion, we have provided empirical proof that well-designed personal-care formulations that act through generic physicochemical mechanism against the basic structure of the virus particle have high virucidal efficacy against the original and evolved SARS-CoV-2 variants. Furthermore, we argue that due to the broad-spectrum mode of action of these tested formulations, the continued practice of good hand hygiene practices with everyday products holds significant promise as an easily accessible, economic, and effective nontherapeutic public health intervention toward reducing the transmission of present and future variants of SARS-CoV-2 across communities and populations.
Published: 2023
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4. Personal care formulations demonstrate virucidal efficacy against multiple SARS-CoV-2 variants of concern: Implications for hand hygiene and public health

Author: Sayandip Mukherjee, Carol K. Vincent, Harshinie W. Jayasekera, and Ashish Shrikant Yekhe
Subjects: Public aspects of medicine, RA1-1270
Abstract: Despite considerable progress being made on vaccine roll out, practicing proper hand hygiene has been advocated as a consistent precautionary intervention against the circulating and emerging variants of SARS-CoV-2. Two variants of concern, namely beta and delta, have been shown to exhibit enhanced transmissibility, high viral load, and ability to escape antibody-mediated neutralization. In this report we have empirically determined the efficacy of selected personal care formulations from Unilever in inactivating the beta and delta variants of SARS-CoV-2 under simulated real-life conditions. All the formulations demonstrated greater than 99.9% reduction in viral infective titres which is comparable to inactivation of the original strain of SARS-CoV-2 virus tested under the same conditions. Therefore, it can be concluded that well-designed personal care formulations when tested under consumer-centric conditions, and with proven efficacy against the parent strain of SARS-CoV-2 will continue to be effective against extant and emerging variants of SARS-CoV-2.
Published: 2022

5. Generation of functional neutrophils from a mouse model of X-linked chronic granulomatous disorder using induced pluripotent stem cells.

Author: Sayandip Mukherjee, Giorgia Santilli, Michael P Blundell, Susana Navarro, Juan A Bueren, and Adrian J Thrasher
Subjects: Medicine, Science
Abstract: Murine models of human genetic disorders provide a valuable tool for investigating the scope for application of induced pluripotent stem cells (iPSC). Here we present a proof-of-concept study to demonstrate generation of iPSC from a mouse model of X-linked chronic granulomatous disease (X-CGD), and their successful differentiation into haematopoietic progenitors of the myeloid lineage. We further demonstrate that additive gene transfer using lentiviral vectors encoding gp91(phox) is capable of restoring NADPH-oxidase activity in mature neutrophils derived from X-CGD iPSC. In the longer term, correction of iPSC from human patients with CGD has therapeutic potential not only through generation of transplantable haematopoietic stem cells, but also through production of large numbers of autologous functional neutrophils.
Published: 2011
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6. Antiviral efficacy of personal care formulations against Severe Acute Respiratory Syndrome Coronavirus 2

Author: Carol K. Vincent, Sayandip Mukherjee, Harshinie W. Jayasekera, and Ashish Shrikant Yekhe
Subjects: medicine.medical_specialty, Alcohol-based sanitizers, Hand Sanitizers, viruses, media_common.quotation_subject, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030231 tropical medicine, Psychological intervention, Soaps, Antiviral Agents, 03 medical and health sciences, 0302 clinical medicine, Hand sanitizer, Hygiene, Humans, Medicine, skin and connective tissue diseases, Intensive care medicine, General Nursing, 030304 developmental biology, media_common, Proper hand, 0303 health sciences, Personal care, SARS-CoV-2, business.industry, Public health, fungi, Public Health, Environmental and Occupational Health, COVID-19, body regions, Infectious Diseases, Alcohols, Virus Inactivation, Handwashes, business, Viral load, Research Paper, Hand Disinfection
Abstract: Background Non-therapeutic interventions such as practicing good hand hygiene continue to be the mainstay of protection from SARS-CoV-2 and other emerging respiratory viruses. Methods We have evaluated a range of commercially available personal care products including soaps, handwash liquids and alcohol-based hand sanitizers for antiviral efficacy against a clinical isolate of SARS-CoV-2 using internationally accepted standardized protocols at user-relevant contact time-points and product dilutions. Results All the tested products resulted in 3 to 4 log reduction of SARS-CoV-2 titer. Conclusion Our data re-affirms recommendations by global public health authorities that proper hand hygiene can reduce SARS-CoV-2 viral load significantly which should likely limit spread of the contagion.
Published: 2021
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7. CPC-containing oral rinses inactivate SARS-CoV-2 variants and are active in the presence of human saliva

Author: Enyia R. Anderson, Edward I. Patterson, Siobhan Richards, Ana K. Pitol, Thomas Edwards, Dominic Wooding, Kate Buist, Alison Green, Sayandip Mukherjee, Michael Hoptroff, and Grant L. Hughes
Subjects: Microbiology (medical), SARS-CoV-2, Mouthwashes, COVID-19, Cetylpyridinium, General Medicine, Microbiology, body regions, stomatognathic system, wc_506, Humans, qw_160, qy_125, Saliva
Abstract: Introduction.The importance of human saliva in aerosol-based transmission of SARS-CoV-2 is now widely recognized. However, little is known about the efficacy of virucidal mouthwash formulations against emergent SARS-CoV-2 variants of concern and in the presence of saliva.Hypothesis.Mouthwashes containing virucidal actives will have similar inactivation effects against multiple SARS-CoV-2 variants of concern and will retain efficacy in the presence of human saliva.Aim.To examinein vitroefficacy of mouthwash formulations to inactivate SARS-CoV-2 variants.Methodology.Inactivation of SARS-CoV-2 variants by mouthwash formulations in the presence or absence of human saliva was assayed using ASTM International Standard E1052-20 methodology.Results.Appropriately formulated mouthwashes containing 0.07 % cetylpyridinium chloride but not 0.2 % chlorhexidine completely inactivated SARS-CoV-2 (USA-WA1/2020, Alpha, Beta, Gamma, Delta) up to the limit of detection in suspension assays. Tests using USA-WA1/2020 indicates that efficacy is maintained in the presence of human saliva.Conclusions.Together these data suggest cetylpyridinium chloride-based mouthwashes are effective at inactivating SARS-CoV-2 variants. This indicates potential to reduce viral load in the oral cavity and mitigate transmission via salivary aerosols.
Published: 2022

8. Personal care formulations demonstrate virucidal efficacy against multiple SARS-CoV-2 variants of concern: implications for hand hygiene

Author: Carol K. Vincent, Harshinie W. Jayasekera, Ashish Shrikant Yekhe, and Sayandip Mukherjee
Subjects: Immune system, Viral envelope, Pandemic, Virulence, Biology, Mode of action, Virology, Viral load, Virus, Neutralization
Abstract: The second and third waves of COVID-19 pandemic have largely been driven by the surge of successive SARS-CoV-2 variants of concern (VOC). These VOC have rapidly spread through multiple geographies being enabled by high transmission rates and/or high viral load compared to the original parent strain. Consequently, the altered phenotypes of these VOC have posed greater challenges to diagnostic and clinical management of COVID-19. Despite considerable progress being made on vaccine roll out, practicing proper hand hygiene has been advocated as a consistent precautionary intervention as more virulent VOC continue to emerge and spread across geographies.Two variants of concern, namely beta and delta, have recently been shown to escape antibody-mediated neutralization by virtue of acquired mutations in the receptor-binding domain of the viral spike protein which binds to the human ACE2 receptor for cellular entry. In this report we have empirically determined the efficacy of a range of personal care formulations in inactivating the beta and delta variants of SARS-CoV-2. High titres of these variants were exposed to marketed personal care formulations from Unilever under standard in-vitro suspension test-based conditions relevant to end-user habits. All the formulations demonstrated greater than 99.9% reduction in viral infective titres. The rate of inactivation by these products were comparable to that of the original strain of SARS-CoV-2 virus tested under the same conditions. Therefore, it can be concluded that well-designed personal care formulations when tested under consumer-centric conditions, and with proven efficacy against the parent strain of SARS-CoV-2 will continue to be effective against extant and emerging variants of SARS-CoV-2. This is through their broad-spectrum mode of action (disruption of lipid bilayer of the host-derived viral envelope, denaturation of envelop and nucleocapsid proteins, and disruption of genome) which is independent of the escape mutations that facilitate immune evasion or enhanced transmissibility.
Published: 2021
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9. Virucidal activity of CPC-containing oral rinses against SARS-CoV-2 variants and are active in the presence of human saliva

Author: Enyia R Anderson, Grant L. Hughes, Sayandip Mukherjee, Michael Hoptroff, Siobhan Richards, Edward I Patterson, and Alison Green
Subjects: 2019-20 coronavirus outbreak, Saliva, Coronavirus disease 2019 (COVID-19), Chemistry, viruses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Chlorhexidine, Cetylpyridinium chloride, Microbiology, body regions, chemistry.chemical_compound, stomatognathic system, medicine, Oral rinses, Oral hygiene products, medicine.drug
Abstract: The role of human saliva in aerosol-based transmission of SARS-CoV-2 has highlighted the need to understand the potential of oral hygiene products to inactivate the virus. Here we examined the efficacy of mouthwashes containing cetylpyridinium chloride (CPC) or chlorhexidine (CHX) in inactivating SARS-CoV-2. After 30 seconds contact under standard aqueous conditions CPC mouthwashes achieved a ≥4.0log10PFU/mL reduction in SARS-CoV-2 (USA-WA1/2020) titres whereas comparable products containing CHX achieved 10PFU/mL reduction. Further testing with CPC mouthwashes demonstrated efficacy against multiple SARS-CoV-2 variants, with inactivation below the limit of detection observed against the Alpha (B.1.1.7), Beta (B.1.351) and Gamma (P.1) variants. Virucidal efficacy of CPC mouthwash was also observed in the presence of human saliva with the product delivering ≥4.0log10PFU/mL reduction in SARS-CoV-2 titres after 30 seconds providing additional evidence for the virucidal efficacy of CPC mouthwashes under simulated physiological conditions. Together these data suggest CPC-based mouthwashes are effective at inactivating SARS-CoV-2 and further supports the use of mouthwash to mitigate the risk of transmission during dentistry procedures.
Published: 2021
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10. Study of J/ψ meson production inside jets in pp collisions at s=8TeV

Author: Shengquan Tuo, Abhigyan Dasgupta, S. Tkaczyk, David Stuart, Alice Mignerey, A. Benecke, Evgenii Tarkovskii, Seth Cooper, Stefanos Leontsinis, Semra Turkcapar, Linda Finco, Tariq Aziz, M. A. Bhat, C. S. Moon, Dave M Newbold, S. Roy Chowdhury, Colin Jessop, Chayanit Asawatangtrakuldee, Guido Tonelli, Vladimir Epshteyn, Sherif Elgammal, Marguerite Tonjes, David Mark Raymond, Olivier Bondu, E. O. Olaiya, Christophe Delaere, Brian L Winer, M. Calderon De La Barca Sanchez, Matthias Kasemann, Zeljko Antunovic, Piergiulio Lenzi, Marko Dragicevic, Fuqiang Wang, Daniel Marley, Sergey Polikarpov, Justin Pilot, Mingshui Chen, Matthias Komm, Arnab Purohit, Wei Zhang, Simona Cometti, Scott Thomas, Cole Lindsey, Paola Salvini, Petr Moisenz, David Ja Cockerill, Wolfgang Lange, Erik Gottschalk, Andrea Delgado, Duncan Leggat, Georgy Antchev, S. W. Lee, J. D. Richman, Yannik Rath, Predrag Cirkovic, Viola Sordini, A. G. Stahl Leiton, Andrej Saibel, Salvatore My, S. Kaplan, Mehmet Özgür Sahin, Donato Creanza, Marc Dobson, Heiner Tholen, Umberto Dosselli, M. Gola, Giacomo Ortona, J. Taylor, J. Kaspar, Alex Kamenev, Victor Kim, Willem Verbeke, Armando Lanaro, Daniel Bloch, Mohamed Rashad Darwish, George Karathanasis, Erika Garutti, Y. Choi, T. A. Gómez Espinosa, Joscha Knolle, Ioanna Papavergou, David Sperka, Gaelle Boudoul, Wolfgang Funk, Vivek Sharma, Giancarlo Mantovani, Carlo Battilana, Brandon Allen, Wolfgang Waltenberger, Florian Beaudette, Dustin Burns, Alexis Kalogeropoulos, Sezen Sekmen, Daniel Arcaro, Prabhat Ranjan Pujahari, Q. Wang, James Hirschauer, James Dolen, Z. Liu, Leonid Chtchipounov, Freya Blekman, Ilse Krätschmer, David Michael Morse, G. Hamel de Monchenault, Inseok Yoon, Marek Walczak, T. Boccali, Riccardo Salvatico, Maurizio Pierini, David Cussans, Giuseppe Benedetto Cerati, Stavros Mallios, James D. Olsen, N. V. Krasnikov, L. J. Sanchez Rosas, Andrea Gelmi, S. Consuegra Rodríguez, K. Osterberg, Urs Langenegger, Aobo Zhang, M. G. Albrow, Christopher Brainerd, Maximilian Heindl, Bora Akgun, Alexander Savin, Aditee Rane, Kai-Feng Chen, Maciej Malawski, Xin Chen, Teresa Rodrigo, Ettore Focardi, M. Finger, Matthieu Marionneau, John Rander, Ulascan Sarica, Maria Toms, Gregor Mittag, Mariana Araujo, J. S. Lange, Mario Maggi, E. A. De Wolf, Salim Cerci, Yuta Takahashi, Adrian Byszuk, Pritam Kalbhor, Rachel Yohay, J. K. Lim, Crisostomo Sciacca, Maxim Goncharov, K. Ehataht, Marco Pieri, F. Simonetto, Sergio P Ratti, Frank Chlebana, Kuntal Mondal, David Fehling, Christoph Garbers, Ian R Tomalin, David Saltzberg, H. Van Haevermaet, Sam Harper, Mykola Savitskyi, Giovanni Organtini, K. Hurtado Anampa, Minseok Oh, Andrés G Delannoy, Christopher Hill, Mikhail Danilov, Alessia Saggio, Vladimir Palichik, Pieter David, Caroline Elisabeth Niniane Niemeyer, J. Park, Alexandre Zabi, Caleb Fangmeier, S. M. A. Ghiasi Shirazi, Vinicius Massami Mikuni, Olga Evdokimov, Junghwan Goh, Livio Fanò, Luigi Guiducci, Gregory R Snow, D. R. Mendis, Paolo Spagnolo, P. Gras, Igor Vorobiev, W. Ji, Claudio Quaranta, Igor Volobouev, Özlem Özçelik, Andris Skuja, Ivica Puljak, Martin Delcourt, Lindsey Gray, John Michael Marraffino, E. De La Cruz-Burelo, Kenneth Call, Francesco Fallavollita, Cesar Augusto Bernardes, Jingzhou Zhao, Julie Managan Hogan, Panos A Razis, Devanjali Dutta, Jennifer Chu, J. H. Kim, Viktor Khristenko, John Gabriel Acosta, Gaël Perrin, Umesh Joshi, J. Mejia Guisao, C. Oropeza Barrera, Sioni Summers, Paul Lujan, Sumit Keshri, Alberto Belloni, D. Horvath, Mohsen Naseri, S. Di Guida, Valeria Botta, M. De Palma, V. Monaco, Thomas Esch, Vladimir Popov, Pushpalatha C Bhat, Nadja Strobbe, Jean-Laurent Agram, G. Paspalaki, Anthony Moeller, C. Barth, Andrius Juodagalvis, I. Dremin, Andrey Popov, P. De Castro Manzano, Anthony Lefeld, Aristotelis Kyriakis, Dong Ho Moon, Adam Elwood, Sami Lehti, Adish Vartak, Welathantri Gd Dharmaratna, Pedro Silva, Regina Demina, Reyer Band, Ferenc Sikler, Mauro Verzetti, Hans Reithler, Mario Kadastik, Alexander Dermenev, Andreas Psallidas, C. Vander Velde, R. Bhattacharya, Shuichi Kunori, Yi Chen, Teresa Lenz, David Bertsche, Valentina Mariani, Ben Bylsma, Roberto Tenchini, Meng Xiao, Giorgia Rauco, Nancy Marinelli, Doris Eckstein, Achim Geiser, Batoul Diab, Rostyslav Shevchenko, Patrick Asenov, Jacopo Pazzini, Virgil E Barnes, Andrzej Novak, David Petyt, Graham Wilson, M. Weber, Y-J Lee, Ivan Shvetsov, Igor Golutvin, Mircho Rodozov, Aruna Nayak, Kerstin Borras, J. H. Yoo, Ketino Kaadze, Jennifer Ngadiuba, Á. Navarro Tobar, Christian Contreras-Campana, E. W. Vaandering, Piet Verwilligen, Nicola Bacchetta, Attila Racz, Roberta Arcidiacono, Christian Schnaible, Jonathan Fulcher, C. Martin Perez, Jan Eysermans, Anatoli Pashenkov, Avto Kharchilava, Mikhail Ignatenko, Tapio Lampén, Jacobo Konigsberg, Attilio Santocchia, Jean Fay, L. J. Gutay, S. Choi, Alexander Spiridonov, I. A. Melzer-Pellmann, Francesca Nessi-Tedaldi, W. Van Doninck, Hans Rykaczewski, Y. J. Mao, Chiara Mariotti, Norraphat Srimanobhas, Yongho Jeong, Marco Monteno, Ohannes Kamer Köseyan, Dermot Moran, David Curry, V. Andreev, Grace Cummings, Sourabh Dube, E. Carrera Jarrin, Douglas Wright, Francesco Fienga, Thoth Gunter, Kirti Ranjan, Milos Dordevic, Carsten Hensel, Gervasio Gomez, Giacomo Fedi, Giles Strong, P. Van Hove, Alice Cocoros, Sayandip Mukherjee, Panagiotis Katsoulis, Laurent Mirabito, Steven Lowette, Korbinian Schweiger, Alessio Ghezzi, Y. Musienko, M. C. Fouz, Samuel Boren, M. M. Defranchis, Matti J Kortelainen, P. Goldenzweig, Abideh Jafari, Johannes Haller, Plamen Iaydjiev, Alexey Volkov, Alexander Morton, Javier Cuevas, Christian Schomakers, Vadim Oreshkin, Atanu Modak, Robert Hirosky, A. Delgado Peris, Andreas Werner Jung, Chandiprasad Kar, Roy Montalvo, Daniel Salerno, R. Sharma, Dong-Chul Son, Liliana Teodorescu, P. Busson, Alexander Titterton, V. Re, Aaron Bundock, Katerina Lipka, Martin Kirakosyan, A. B. Meyer, Burak Bilki, Marco Cipriani, Peter Elmer, Rohan Bhandari, Vinay Hegde, David Zou, Nicolò Trevisani, Stephan Albert Wiederkehr, F. M. Stober, Anna Kropivnitskaya, A. García Alonso, Dirk Krücker, Gianluca Cerminara, Marcella Diemoz, Vipin Bhatnagar, T. Liu, Rishika Bhardwaj, Lorenzo Russo, Simon Christoph Schuler, Anadi Canepa, Dario Menasce, Alessio Boletti, Jie Zhang, Francesca Romana Cavallo, János Karancsi, Ali Celik, Viktor Savrin, Mitchell Wayne, Karol Bunkowski, P. de Barbaro, Cheng-Chieh Peng, Marcello Abbrescia, Sabino Meola, Roberto Covarelli, Sergio Cittolin, Jared Sturdy, Stephen Mrenna, Denys Lontkovskyi, Konstantinos Manolopoulos, Andrey Korytov, P. Chang, Georgios Bakas, Stephen Sanders, Alberto Santoro, H. S. Kim, Sanjay Kumar, Kaya Tatar, A. Bornheim, Peisen Ma, Christopher Mcginn, Sandra S. Padula, Yiwen Wen, Paolo Vitulo, Maximilian Knut Kiesel, William J Spalding, Jay Roberts, Stefano Bianco, Brandon Chiarito, Markus Stoye, A. Escalante Del Valle, Joosep Pata, C. Wissing, A. Castaneda Hernandez, Dooyeon Gyun, Francesca Cavallari, Sridhara Dasu, Emilio Meschi, M. Flechl, Mikhail Dubinin, G. Cucciati, M. J. Kim, Tanvi Wamorkar, Eshwen Bhal, Paolo Dini, S. Bheesette, Colin Bernet, Dimitri Bourilkov, Marc Weinberg, Fabio Ravera, Maren Tabea Meinhard, S. W. Cho, Andrew Whitbeck, Eduardo De Moraes Gregores, Wei Li, Demetra Tsiakkouri, Shawn Zaleski, Danila Tlisov, Suat Ozkorucuklu, Rishi Patel, Y. D. Oh, Simranjit Singh Chhibra, Ashfaq Ahmad, F. Vazquez Valencia, Clément Leloup, Santeri Laurila, Alexander Nikitenko, Ashim Roy, Th. Müller, Jasvinder A. Singh, M. Rahmani, Daniel Robert Marlow, Thea Klaeboe Aarrestad, Viktor Veszpremi, Alexander Schmidt, Ali Eren Simsek, Eric Conte, David Barney, Aleksandra Lelek, Stephanie Beauceron, Joshua Kunkle, Grigory Safronov, Ulrich Husemann, Yousen Zhang, W. T. Lin, Dylan Hsu, Wei Xie, Rainer Wallny, V. Drugakov, Andre Frankenthal, Raman Khurana, Adel Terkulov, Jan Krolikowski, Luiz Mundim, A. Manousakis-Katsikakis, Fabio Monti, Giorgio Maggi, Sadia Khalil, Haiyan Wang, C. Fernandez Bedoya, S. Van Putte, Stefan Grünendahl, Diogo Bastos, S. Baur, Yves Sirois, Robert Schöfbeck, Guillaume Bourgatte, Mehmet Oglakci, Fanbo Meng, Caroline Collard, Lei Feng, L. Malgeri, Kamuran Dilsiz, Seema Bahinipati, Paolo Rumerio, Meena Meena, Alexei Safonov, C.-E. Wulz, Duccio Abbaneo, Marco Zanetti, Li Li, U. Bhawandeep, Tae Jeong Kim, Emmanouil Vourliotis, Lorenzo Uplegger, Marius Teroerde, Rogelio Reyes-Almanza, Georgios Anagnostou, Melody A. Swartz, Maxwell Chertok, Danek Kotlinski, Jordan Martins, Ugur Kiminsu, A. Melo, Georgia Karapostoli, Martti Raidal, Alexandros Attikis, Gabriel Madigan, Piero Giorgio Verdini, Philip Harris, D. Matos Figueiredo, Noemi Beni, A. Perrotta, Emanuela Barberis, Nikola Godinovic, Hualin Mei, Altan Cakir, Paolo Meridiani, Aron Soha, Simon Kurz, Michael Dittmar, Michael Murray, Jakob Salfeld-Nebgen, Sarah Freed, I. Gonzalez Caballero, Sebastian Wiedenbeck, Kunal Kothekar, Alicia Calderon, Shabnam Jabeen, T. Aushev, Thomas Reitenspiess, Pamela Klabbers, Ivan Amos Cali, A. Carvalho Antunes De Oliveira, Caglar Zorbilmez, Nadir Daci, Tengizi Toriashvili, S. Bhattacharya, P. C. Tiwari, Elizabeth Locci, Ilaria Vai, Janos Erö, Emrah Tiras, Toyoko Orimoto, Cristina Biino, Gabriele Benelli, Patrizia Barria, Julia Velkovska, Kevin Mcdermott, Dmytro Kovalskyi, Seyed Mohsen Etesami, Giovanni Mocellin, V. Kutzner, Bolek Wyslouch, Gyorgy Vesztergombi, Ali Harb, Rizki Syarif, Ia Iashvili, Jean-Roch Vlimant, Brajesh C Choudhary, Paul David Luckey, Emanuele Usai, H. S. Chen, Yury Ivanov, Andre Sznajder, Serdal Damarseckin, Norbert Neumeister, Maria Spiropulu, Alexander Fröhlich, Christian Autermann, Bradley Cox, Somnath Choudhury, Marco Trovato, Sébastien Viret, Junquan Tao, O. Kukral, Sandra Oliveros, Alfredo Gurrola, Ufuk Guney Tok, K. S. Lee, M. Della Negra, Maria Isabel Josa, M. Tadel, Christopher Brew, Gintautas Tamulaitis, Iuri Bagaturia, A. P. Singh, Yuri Gershtein, Denis Gelé, Catherine Schiber, Mauro Emanuele Dinardo, Carmen Albajar, Sven Dildick, Nhan Viet Tran, Mohammad Abrar Wadud, Abhisek Datta, O. Hlushchenko, Sudha Ahuja, Halil Saka, Pietro Govoni, Patrick Jarry, Kenneth Bloom, Thomas Perry, M. De Mattia, Siddhesh Sawant, J. D. Lewis, Benjamin Charles Radburn-Smith, Kevin Nash, Joona Havukainen, Nazar Bartosik, Lothar At Bauerdick, Leonardo Giannini, G. Quast, A. Bat, Elizabeth Starling, Nan Lu, René Caspart, Burin Asavapibhop, Xunwu Zuo, James Bueghly, Matthew Nguyen, Philip Baringer, Enrico Robutti, George Stephans, Eva Halkiadakis, Elisabetta Manca, Christoph Grab, Tiziano Rovelli, Frank Jm Geurts, Smarajit Karmakar, Weinan Si, Samila Muthumuni, Maciej Misiura, Gilvan Alves, M. Pelliccioni, Anna Teresa Meneguzzo, K. Wong, Yen-Jie Lee, S. Nandan, A. De Iorio, Pietro Vischia, Fionn Ball, Angelo Giacomo Zecchinelli, G. P. Van Onsem, Zaixing Mao, Doga Gulhan, Louis Lyons, Christian Dorfer, Roberto Dell'Orso, Gregor Kasieczka, Matthew Herndon, Gourab Saha, Valentina Dutta, Aleksandar Aleksandrov, J. W. Gary, Arnaud Steen, Robert M Harris, G. Correia Silva, Elliot Hughes, D. A. Sanz Becerra, Andrew Buccilli, Charles C. Richardson, James Bowen, Arun Kumar, Elisabetta Gallo, Vincenzo Ciriolo, Elisa Fontanesi, G. Kozlov, Thomas James, Sevgi Tekten, O. Gonzalez Lopez, N. Zaganidis, Cecilia Elena Gerber, Francisco Matorras, S. Banerjee, John A Coughlan, Camille Camen, Andres Tiko, D. Domínguez Damiani, A. M. Rossi, Frank Glege, P. Das, Diego Beghin, Olivér Surányi, Paul Sheldon, Olena Karacheban, Hannsjoerg Artur Weber, I. Babounikau, A. Ranieri, Livia Soffi, Jovan Milosevic, R. B. Garg, Christopher Seez, Jacob Linacre, Yongbin Feng, Bernard Ille, Y. Chao, G. B. Yu, Y. 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Medina Jaime, Elizabeth Kennedy, Margaret Zientek, Unki Yang, Ozgun Kara, Patrick Connor, Giovanna Selvaggi, Daniel Gastler, Daniel Abercrombie, Alain Givernaud, Seth Moortgat, P. Sphicas, Muhammad Waqas, Izaak Neutelings, Predrag Milenovic, Peter R Hobson, Kin Ho Lo, E. Eskandari Tadavani, Sudarshan Paramesvaran, Victor Daniel Elvira, Bilal Kiani, Gabor Istvan Veres, Alexander Snigirev, F. Hartmann, Stephane Cooperstein, S. Ragazzi, John Strologas, J. Fernandez Menendez, Charles Maguire, J. R. González Fernández, Clemens Wöhrmann, Yeonju Go, A. Vagnerini, Christophe Ochando, Francesco Santanastasio, Stoyan Stoynev, A. Sanchez-Hernandez, Tongguang Cheng, Sergo Jindariani, J. Schwandt, M. Ruspa, Caleb Smith, Florian Michael Pitters, John Hakala, Stephanie Kwan, Sarah Catherine Eno, Jan-Frederik Schulte, Alexander Bylinkin, Vladislav Borchsh, D. Kim, Daniel Teyssier, Victor Perelygin, Manisha Lohan, Alessandra Fanfani, J. Duarte Campderros, Frixos A Triantis, Andrew Askew, R. L. Lander, Nicholas Menendez, M. Olmedo Negrete, Miao Hu, Hugues Brun, Pieter Everaerts, Titas Roy, Alexx Perloff, Roman Ryutin, Federica Primavera, Roberto Carlin, Pierre Depasse, Vyacheslav Klyukhin, M. Van De Klundert, Victor Golovtcov, Sören Erdweg, Luisa Benussi, Richard B. Lipton, Kurt Jung, J. Seixas, Merve Ince, Etiennette Auffray, Maurizio Biasini, D. R. Muller, A. Yagil, Sinan Sagir, Marta Felcini, Nikitas Loukas, Mani Tripathi, Rachel Bartek, Marco Peruzzi, Usama Hussain, Owen Rosser Long, Warren Clarida, Dana Z. Anderson, Cesare Calabria, M. Csanad, Nicola Amapane, A. Di Crescenzo, Lalit Mohan Pant, Andreas Nowack, Aaron Dominguez, Felicitas Pauss, Angira Rastogi, Ayse Polatoz, Austin Baty, Shin-Shan Yu, Wenxing Fang, Geoffrey Hall, William Mcbrayer, G. N. Kim, Georgios Tsipolitis, Sanjay Padhi, B. Chazin Quero, Dener De Souza Lemos, Panagiotis Kokkas, S. K. Pflitsch, Koushik Mandal, Niels Dupont, Zhengcheng Tao, Gy L. Bencze, J. M. Hernandez, Edward Laird, Aurore Savoy-Navarro, Luca Mastrolorenzo, Vieri Candelise, Ted Kolberg, C. Uribe Estrada, Muhammad Shoaib, Claude Charlot, Reddy Pratap Gandrajula, Ibrahim Soner Zorbakir, Michael Reichmann, David Vannerom, Giuseppe Iaselli, Georgi Sultanov, Evan Wolfe, Kevin Stenson, C. Mora Herrera, B. Singh, M. Mohammadi Najafabadi, Anton Babaev, Charles Harrington, Emil Sørensen Bols, Panja-Riina Luukka, Dennis Noll, Alberto Benvenuti, Roberto Salerno, Scarlet Norberg, Olga Kodolova, Ram Krishna Dewanjee, Bora Isildak, Daniel Winterbottom, N. Cavallo, Po-Hsun Chen, Stefano Mersi, Mykyta Haranko, Maria Agnese Ciocci, Maria Florencia Canelli, Fabrizio Ferro, Thomas Ferbel, Tom A. Williams, D. Y. Wang, Tobias Pook, Jay Hauser, A. Vilela Pereira, Stepan Obraztsov, Anshul Kapoor, Christophe Royon, Elizabeth Sexton-Kennedy, A. Álvarez Fernández, R. Kumar Verma, Bobae Kim, Narumon Suwonjandee, Kun Shi, Matthias Wolf, Paolo Ronchese, Badder Marzocchi, Sanjay Kumar Swain, Marc M Baarmand, Daniele Trocino, A. Stahl, Ian Laflotte, C. Mills, Gabriella Pugliese, Biagio Rossi, Winston Ko, I. De Bruyn, Reza Goldouzian, Mohd Nizam Yusli, Kevin Lannon, Renato Potenza, G. Della Ricca, Andrew Carnes, Guenter Eckerlin, Armen Tumasyan, Paula Eerola, Manoj Sharan, Claudio Caputo, Guenakh Mitselmakher, C. E. Flores, Rui Xiao, Kevin Burkett, J. Lykken, Pasquale Musella, S. Orfanelli, Jordan Damgov, D. Di Croce, Peter Hansen, Yangyang Cheng, Andrea Bocci, Kisung Lee, Francisco Garcia, Basile Vermassen, Jay Mathew Lawhorn, Claude Amsler, Brent Yates, Andrea Bellora, Sihyun Jeon, Pirmin Berger, Tommaso Dorigo, Sandra Malvezzi, W. L. Prado Da Silva, Laurent Favart, Cristian Pena, Thomas Reis, Pietro Faccioli, D. H. Kim, Martin Lipinski, Frank Würthwein, Alberto Zucchetta, V. Petrov, Shao Min Tan, Manas Maity, Alexi Mestvirishvili, Ulrich Goerlach, Ivan Reid, Christine Mclean, Anastasia Grebenyuk, G. Dissertori, Joze Zobec, Massimo Casarsa, Steve Nahn, Marco Meschini, Paolo Capiluppi, Frigyes Nemes, James Rohlf, Konstantin Androsov, Carlos Avila, Sergei Bitioukov, Marino Missiroli, Ricardo Eusebi, William Tabb, C. Neu, Dmitry Hits, Jorma Tuominiemi, Thong Nguyen, Y. C. Yang, Guillaume Falmagne, Imad Baptiste Laktineh, Lucas Taylor, Matthew Citron, G. De Lentdecker, Lin Wang, David Overton, Sang Il Pak, Marco Cuffiani, Roberto Sacchi, Oliver Buchmuller, Cameron Bravo, Tejinder Virdee, Nicolò Tosi, M. Jones, Camilla Galloni, Seth Conrad Zenz, I. Heredia-De La Cruz, Vincenzo Daponte, M. Vidal Marono, Julia Thom, Finn Rebassoo, Volker Blobel, Jian Sun, Alibordi Muhammad, Artur Kalinowski, Joshua Hardenbrook, Neeti Parashar, W. T. Hung, Klaus Rabbertz, Sebastiano Albergo, Igor Lokhtin, Myriam Schönenberger, Zachary Lesko, Marco Alexander Harrendorf, Fábio Lúcio Alves, Efe Yazgan, Luciano Orsini, Luca Pacher, Claire Shepherd-Themistocleous, Michael Wassmer, Antonis Agapitos, Thi Hien Doan, Daniel Denegri, Magda Diamantopoulou, Hartmut Stadie, Natascha Krammer, S. J. Qian, F. Gasparini, M. R. Adams, Giuseppe Codispoti, M. Guchait, Fatma Boran, Elena Voevodina, Ioannis Papakrivopoulos, Laurent Thomas, Mark Derdzinski, Victor Murzin, Q. Li, Miaoyuan Liu, Katja Klein, Jens Multhaup, R. F. Harr, Ashish Sharma, Markus Radziej, Roberto Mulargia, Dylan Gilbert, Navid Rad, Yagya Raj Joshi, Alessandro Caratelli, Natale Demaria, Susan Gascon, Gunther Roland, K. El Morabit, Ji Hwan Bhyun, Illia Khvastunov, N. Turini, Jeremie Alexandre Merlin, Piotr Zalewski, C. Kleinwort, Lea Caminada, Rong-Shyang Lu, Xinmei Niu, Dragos Velicanu, Qamar Hassan, Nuno Leonardo, Simon Regnard, Jiajing Mao, Leonid Levchuk, B. Penning, Luca Scodellaro, Christos Roskas, Maria Cepeda, Ashutosh Bhardwaj, Jorgen D'Hondt, Davide Piccolo, Kelly Beernaert, T. Mitchell, Bahareh Roozbahani, Nadeesha Wickramage, Peter Raics, Peicho Petkov, Anna Zanetti, Q. Ingram, L. Valencia Palomo, Leonardo Cristella, Achille Petrilli, Chun-Hua Jiang, Paul Avery, Salavat Abdullin, Lisa Benato, Quentin Python, Randy Ruchti, Joe Incandela, Sushil Chauhan, Kajari Mazumdar, Nickolas Mccoll, Luca Cadamuro, Gobinda Majumder, H. Rejeb Sfar, Jane Nachtman, R. Gonzalez Suarez, Sergio F Novaes, Samet Lezki, Morgan Lethuillier, Yasar Onel, Marcus Hohlmann, Sharad Malik, Carlos Florez, Amedeo Staiano, Nicolas Postiau, Ignacio Redondo, Benjamin Stieger, Marco Musich, A. De Cosa, Hannes Sakulin, Tilman Rohe, Jing Wang, Sara Nabili, M. Bluj, Yurii Maravin, Vladimir Gavrilov, H. Sert, Hongbo Liao, Aleko Khukhunaishvili, Stefano Marcellini, Sonaina Undleeb, Spandan Mondal, Laura Dodd, Andrew Levin, Anton Stepennov, A. C. Le Bihan, R. M. Brown, Hannes Jung, Mark Saunders, Andrew Loeliger, Andrey Gribushin, Ashley Parker, D. H. Miller, Filippo Errico, Deepak Kumar Sahoo, Jean-Louis Faure, Philipp Millet, Alexander Zhokin, Martijn Mulders, A. Rose, S. Kaur, A. Bragagnolo, Brian Francis, Tamas Ferenc Csorgo, Paolo Checchia, Alberto Messineo, John Almond, Song-Ming Wang, Kamal Lamichhane, Mary Hadley, Nicholas Eminizer, Daniele Ruini, Martino Margoni, Michail Bachtis, Bennett Marsh, Duncan Carlsmith, Manfred Paulini, Jessica Prisciandaro, Pierluigi Bortignon, Ugo Gasparini, Veikko Karimäki, Zaixin Wang, Sara Fiorendi, Vasken Hagopian, G. M. Dallavalle, Bhargav Madhusudan Joshi, Georgios Krintiras, Matteo Presilla, Zeynep Demiragli, Marina Kolosova, Yalcin Guler, Roger Wolf, Lev Dudko, Jeremy Andrea, Marta Verweij, Hong Ni, W. T. Ford, P. J. Fernández Manteca, Luca Guzzi, Pierluigi Zotto, Hwi Dong Yoo, Robert Bainbridge, Julie Malcles, Fengwangdong Zhang, A. Scribano, Yi-ting Duh, and Boris Grynyov
Subjects: Physics, Quantum chromodynamics, Nuclear and High Energy Physics, Jet (fluid), Particle physics, Large Hadron Collider, Luminosity (scattering theory), Meson, 010308 nuclear & particles physics, Astrophysics::High Energy Astrophysical Phenomena, Nuclear Theory, High Energy Physics::Phenomenology, Function (mathematics), 01 natural sciences, Pseudorapidity, 0103 physical sciences, High Energy Physics::Experiment, Rapidity, Nuclear Experiment, 010306 general physics
Abstract: A study of the production of prompt J / ψ mesons contained in jets in proton-proton collisions at s = 8 TeV is presented. The analysis is based on data corresponding to an integrated luminosity of 19.1 fb−1 collected with the CMS detector at the LHC. For events with at least one observed jet, the angular separation between the J / ψ meson and the jet is used to test whether the J / ψ meson is part of the jet. The analysis shows that most prompt J / ψ mesons having energy above 15 GeV and rapidity | y | 1 are contained in jets with pseudorapidity | η jet | 1 . The differential distributions of the probability to have a J / ψ meson contained in a jet as a function of jet energy for a fixed J / ψ energy fraction are compared to a theoretical model using the fragmenting jet function approach. The data agree best with fragmenting jet function calculations that use a long-distance matrix element parameter set in which prompt J / ψ mesons are predicted to be unpolarized. This technique demonstrates a new way to test predictions for prompt J / ψ production using nonrelativistic quantum chromodynamics.
Published: 2020
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11. Gene therapy for PIDs: Progress, pitfalls and prospects

Author: Sayandip Mukherjee and Adrian J. Thrasher
Subjects: NADPH, nicotinamide adenine dinucleotide phosphate hydrogen, Adenosine Deaminase, ADA-SCID, adenosine deaminase deficiency-severe combined immunodeficiency, XLN, X-linked neutropenia, Genetic enhancement, MN, meganucleases, Review, Bioinformatics, Granulomatous Disease, Chronic, X-Linked Combined Immunodeficiency Diseases, miR, microRNA, SIN, self-inactivating, 0302 clinical medicine, NK cells, natural killer cells, Agammaglobulinemia, RVs, retroviral vectors, Transgenes, HSCs, haematopoietic stem cells, 0303 health sciences, Clinical Trials as Topic, GALV, gibbon ape leukaemia virus, UCOE, ubiquitous chromatin opening element, Hematopoietic Stem Cell Transplantation, General Medicine, GSH, genomic safe harbour, 3. Good health, ERT, enzyme replacement therapy, LVs, lentiviral vectors, 030220 oncology & carcinogenesis, HSCT, MDS, myelodysplastic syndrome, SCID-X1, X-linked severe combined immunodeficiency, WAS, Transgene, DSB, double strand break, GvHD, graft versus host disease, CGD, chronic granulomatous disorder, PGK, phosphoglycerokinase, Biology, HSCT, haematopoietic stem cell transplant, SCID, Transplantation, Autologous, Viral vector, 03 medical and health sciences, ROS, reactive oxygen species, Gene therapy, WAS, Wiskott–Aldrich syndrome, XLT, X-linked thrombocytopenia, CGD, ZFN, zinc finger nuclease, medicine, Genetics, Humans, IFN, interferon, TALEN, transcription activator-like effector nucleases, T-ALL, T cell-acute lymphoblastic leukaemia, 030304 developmental biology, PEG, polyethylene glycol, Severe combined immunodeficiency, SAE, serious adverse event, HLA, human leukocyte antigen, VSV-G, vesicular stomatitis virus-G protein, WASp, Wiskott–Aldrich syndrome protein, PID, Immunologic Deficiency Syndromes, MLV, murine leukaemia virus, Genetic Therapy, medicine.disease, Hematopoietic Stem Cells, IL, interleukin, Clinical trial, Transplantation, Mutagenesis, Insertional, Immunology, Primary immunodeficiency, Severe Combined Immunodeficiency, PIDs, primary immunodeficiency disorders, LTR, long terminal repeat, EF-1α, elongation factor 1α, HR, homologous recombination, SFFV, spleen focus-forming virus, LCR, locus control region
Abstract: Substantial progress has been made in the past decade in treating several primary immunodeficiency disorders (PIDs) with gene therapy. Current approaches are based on ex-vivo transfer of therapeutic transgene via viral vectors to patient-derived autologous hematopoietic stem cells (HSCs) followed by transplantation back to the patient with or without conditioning. The overall outcome from all the clinical trials targeting different PIDs has been extremely encouraging but not without caveats. Malignant outcomes from insertional mutagenesis have featured prominently in the adverse events associated with these trials and have warranted intense pre-clinical investigation into defining the tendencies of different viral vectors for genomic integration. Coupled with issues pertaining to transgene expression, the therapeutic landscape has undergone a paradigm shift in determining safety, stability and efficacy of gene therapy approaches. In this review, we aim to summarize the progress made in the gene therapy trials targeting ADA-SCID, SCID-X1, CGD and WAS, review the pitfalls, and outline the recent advancements which are expected to further enhance favourable risk benefit ratios for gene therapeutic approaches in the future., Highlights • PID gene therapy is a promising alternative to HSCT in absence of suitable donors. • Gene therapy clinical trials targeting various PIDs have shown significant efficacy. • Retroviral and lentiviral vectors are presently the mainstay of gene delivery. • Insertional mutagenesis and vector silencing constitute the main concerns. • Novel gene delivery approaches are currently being investigated and validated.
Published: 2013
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12. Brief Report: Self-Organizing Neuroepithelium from Human Pluripotent Stem Cells Facilitates Derivation of Photoreceptors

Author: Robin R. Ali, Sayandip Mukherjee, Adrian J. Thrasher, Cédric Boucherie, Jane C. Sowden, and Els Henckaerts
Subjects: Photoreceptors, ROD PHOTORECEPTORS, genetic structures, Cellular differentiation, Gene Expression, MOUSE, Retinal Rod Photoreceptor Cells, Induced pluripotent stem cell, Cells, Cultured, PRECURSORS, Cell Differentiation, Hematology, Extracellular matrix, Anatomy, NUCLEAR RECEPTOR NR2E3, Extracellular Matrix, Cell biology, Neuroepithelial cell, Drug Combinations, DIFFERENTIATION, medicine.anatomical_structure, Oncology, Molecular Medicine, Proteoglycans, Collagen, Life Sciences & Biomedicine, EXPRESSION, Pluripotent Stem Cells, GENES, Genetic Vectors, Biology, Time-Lapse Imaging, Retina, Directed differentiation, Cell & Tissue Engineering, Retinitis pigmentosa, Induced pluripotent, medicine, Humans, Hedgehog Proteins, RETINAL PROGENITOR CELLS, Eye Proteins, Homeodomain Proteins, Science & Technology, TRANSPLANTATION, Lentivirus, Cell Biology, Fibroblasts, medicine.disease, Embryonic stem cell, eye diseases, Three-dimensional culture, Fibroblast Growth Factors, Biotechnology & Applied Microbiology, Trans-Activators, Laminin, sense organs, Embryonic, Biomarkers, GENERATION, Developmental Biology
Abstract: Retinitis pigmentosa, other inherited retinal diseases, and age-related macular degeneration lead to untreatable blindness because of the loss of photoreceptors. We have recently shown that transplantation of mouse photoreceptors can result in improved vision. It is therefore timely to develop protocols for efficient derivation of photoreceptors from human pluripotent stem (hPS) cells. Current methods for photoreceptor derivation from hPS cells require long periods of culture and are rather inefficient. Here, we report that formation of a transient self-organized neuroepithelium from human embryonic stem cells cultured together with extracellular matrix is sufficient to induce a rapid conversion into retinal progenitors in 5 days. These retinal progenitors have the ability to differentiate very efficiently into Crx(+) photoreceptor precursors after only 10 days and subsequently acquire rod photoreceptor identity within 4 weeks. Directed differentiation into photoreceptors using this protocol is also possible with human-induced pluripotent stem (hiPS) cells, facilitating the use of patient-specific hiPS cell lines for regenerative medicine and disease modeling. ispartof: STEM CELLS vol:31 issue:2 pages:408-414 ispartof: location:England status: published
Published: 2013
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13. Valproic Acid Confers Functional Pluripotency to Human Amniotic Fluid Stem Cells in a Transgene-free Approach

Author: Joris Vermeesch, Sayandip Mukherjee, Gudrun E. Moore, Anthony Atala, Adrian J. Thrasher, Gemma N. Jones, Jennifer M. Frost, Nicholas M. Fisk, Michael P. Blundell, Pascale V. Guillot, Daniel Nettersheim, T Selvee Ramasamy, Kenneth Lay, Beata Nowakowska, Mara Cananzi, Dafni Moschidou, Paolo De Coppi, Hassan Abdulrazzak, Anju Phoolchund, James Adjaye, Mark H.F. Sullivan, Katharina Drews, and Hubert Schorle
Subjects: Male, Rex1, Induced Pluripotent Stem Cells, Embryoid body, Biology, 03 medical and health sciences, 0302 clinical medicine, Drug Discovery, Genetics, Humans, Induced pluripotent stem cell, Cell potency, Molecular Biology, 030304 developmental biology, Pharmacology, 0303 health sciences, Induced stem cells, Valproic Acid, Amniotic Fluid, Molecular biology, Embryonic stem cell, Cell biology, Histone Deacetylase Inhibitors, 030220 oncology & carcinogenesis, Molecular Medicine, Original Article, Female, Stem cell, Reprogramming
Abstract: Induced pluripotent stem cells (iPSCs) with potential for therapeutic applications can be derived from somatic cells via ectopic expression of a set of limited and defined transcription factors. However, due to risks of random integration of the reprogramming transgenes into the host genome, the low efficiency of the process, and the potential risk of virally induced tumorigenicity, alternative methods have been developed to generate pluripotent cells using nonintegrating systems, albeit with limited success. Here, we show that c-KIT+ human first-trimester amniotic fluid stem cells (AFSCs) can be fully reprogrammed to pluripotency without ectopic factors, by culture on Matrigel in human embryonic stem cell (hESC) medium supplemented with the histone deacetylase inhibitor (HDACi) valproic acid (VPA). The cells share 82% transcriptome identity with hESCs and are capable of forming embryoid bodies (EBs) in vitro and teratomas in vivo. After long-term expansion, they maintain genetic stability, protein level expression of key pluripotency factors, high cell-division kinetics, telomerase activity, repression of X-inactivation, and capacity to differentiate into lineages of the three germ layers, such as definitive endoderm, hepatocytes, bone, fat, cartilage, neurons, and oligodendrocytes. We conclude that AFSC can be utilized for cell banking of patient-specific pluripotent cells for potential applications in allogeneic cellular replacement therapies, pharmaceutical screening, and disease modeling. ispartof: Molecular Therapy vol:20 issue:10 pages:1953-1967 ispartof: location:United States status: published
Published: 2012
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14. Progress and Prospects: Advancements in Retroviral Vector Design, Generation, and Application

Author: Sayandip Mukherjee and Adrian J. Thrasher
Subjects: Genetics, Transgene, Genetic Vectors, Lentivirus, Gene Transfer Techniques, Biology, Long terminal repeat, Viral vector, Insertional mutagenesis, Transduction (genetics), Gene Expression Regulation, Molecular Medicine, Genetic Engineering, Enhancer, Molecular Biology, Gene, Selectable marker
Abstract: lthough gammaretroviruses have been hugely im-portant for proof-of-principle demonstrations of efﬁcacyin several speciﬁc clinical applications, other retroviral clas-ses, lentiviruses in particular, are emerging as promisingalternatives. Of the on-going 35 trials using lentivirus-basedvectors (LVs), 24 are in phase I, 9 in phase I/II, and 1 each inphases II and III (source: http://clinicaltrials.gov/). In ad-dition to their ability to stably integrate into the genome oftarget cells for long-term expression of the gene of interest,LVs enjoy a few signiﬁcant advantages through their abilityto transduce nondividing cells and also to allow robusttransgene expression in cells where there is a high proba-bility of epigenetic silencing or position-related variation ofactivity (Trono, 2000; Schambach and Baum, 2008). Early-generation gammaretroviral vectors have been shown to beparticularly prone to insertional mutagenesis through inad-vertent long terminal repeat (LTR)-mediated upregulationof proto-oncogene expression (Ott et al., 2006; Hacein-Bey-Abina et al., 2008; Howe et al., 2008; Stein et al., 2010). Inpart, this risk may be enhanced by the intrinsic preference ofthese vectors to integrate in and around gene regulatoryregions. LVs may therefore have an overall safer integrationproﬁle, although both exhibit a semirandom pattern of in-sertion into the human genome, and this type of risk stillcannot be ignored (Bushman et al., 2005; Cavazzana-Calvoet al., 2010). The safety of LVs has been enhanced in severalways including self-inactivating (SIN) vector design, tat in-dependence, use of insulators, and employment of internaltissue- or lineage-speciﬁc promoter and enhancer sequences,thereby reducing risks of insertional mutagenesis and vectormobilization (Matrai et al., 2010). Even so, longer term ob-servations in the clinical arena will be needed to deﬁne therisk for newer integrating vectors with more clarity. Con-currently, the development of a stable packaging cell line toensure useful batch consistency and size during large-scaleclinical vector production and puriﬁcation under strict GoodManufacturing Practice (GMP) conditions has been at-tempted by various groups. Inducible systems for generatingstable cell lines have been developed to eliminate cytotox-icity from viral gene products required for packaging, suchas the HIV-1-derived protease and Rev, and the heter-ologous VSV-G envelope protein (Xu et al., 2001; Ikeda et al.,2003; Cockrell et al., 2006; Broussau et al., 2008; Kutner et al.,2009; Throm et al., 2009). It is also noteworthy thatreplication-competent LVs (generated by homologous re-combination between packaging and vector constructs) havenot been detected in large-scale production batches based onlatest generation packaging systems and vector design(Merten et al., 2011). In this commentary, we comment on sixoriginal research articles addressing three separate areasrelating to continuing efforts in improving retroviral design,production, and application for preclinical research andclinical applications.In this issue of Human Gene Therapy, Marc Giry-Laterrie`reand colleagues describe a modiﬁed tetracycline (TET)-inducible, polycistronic vector system encoding a selectablemarker and allowing for simple transgene cloning. As notedin their paper, the individual features incorporated in the‘‘polyswitch vector’’ have been previously described byseveral groups. The novelty lies in the combination of thesein a single vector to facilitate stable, inducible, and reversibletransgene expression from a single integration event. Sincethe description of the ﬁrst tetracycline-inducible system byGossen and Bujard (1992), various small-molecule inducersystems have been employed to control the levels and timingof transgene expression both in vitro and in vivo (Vigna et al.,2002; Sirin and Park, 2003; Galimi et al., 2005). However,many have suffered from either low levels of inducibility orleakiness in the absence of the speciﬁc inducer. The modiﬁedpTF promoter used in this current study was shown to havelow basal activity and high inducibility. The authors alsoseparated a selectable marker (regulated by a ubiquitoushuman elongation factor-1a promoter) from the inducibletransgene cassette for enrichment of transduced cells beforeactivating the transgene of interest, and were able to dem-onstrate regulated expression from their vector in cell lines aswell as primary human cells. Of course, it will now beimportant to evaluate the performance of this vector inpreclinical animal models, especially in terms of drug in-ducibility and reversibility on withdrawal. Although this islikely to be useful for a number of applications, there willalso be restrictions on the nature of the transgene dictated
Published: 2011
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15. High Rate of Genetic Recombination in Murine Leukemia Virus: Implications for Influencing Proviral Ploidy

Author: Jianling Zhuang, Sayandip Mukherjee, Joseph P. Dougherty, and Yacov Ron
Subjects: viruses, Immunology, Microbiology, Genetic recombination, Virus, Chromosomal crossover, Mice, Virology, Murine leukemia virus, Animals, Humans, Crossing Over, Genetic, Gammaretrovirus, Genetics, Ploidies, biology, Virus Assembly, RNA, Provirus, biology.organism_classification, Genetic Diversity and Evolution, Insect Science, HIV-1, NIH 3T3 Cells, RNA, Viral, Moloney murine leukemia virus, Recombination, HeLa Cells
Abstract: A significant difference in the recombination rates between human immunodeficiency virus type 1 (HIV-1) and the gammaretroviruses was previously reported, with the former being 10 to 100 times more recombinogenic. It is possible that preferential copackaging of homodimers in the case of gammaretroviruses, like murine leukemia virus (MLV), led to the underestimation of their rates of recombination. To reexamine the recombination rates for MLV, experiments were performed to control for nonrandom copackaging of viral RNA, and it was found that MLV and HIV-1 exhibit similar crossover rates. The implications for control of proviral ploidy and preferential recombination during minus-strand DNA synthesis are discussed.
Published: 2006
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16. iPSCs: Unstable Origins?

Author: Adrian J. Thrasher and Sayandip Mukherjee
Subjects: Pharmacology, Autologous cell, Induced Pluripotent Stem Cells, High resolution, Gene transfer, Computational biology, Epigenome, Biology, Bioinformatics, Cellular Reprogramming, Peripheral blood, Genomic Instability, Epigenesis, Genetic, MicroRNAs, Drug Discovery, Commentary, Genetics, Humans, Molecular Medicine, Induced pluripotent stem cell, Reprogramming, Molecular Biology, Epigenesis
Abstract: The advent of induced pluripotent stem cell (iPSC) technology holds great promise to revolutionize personalized cell-based therapies.1,2,3,4,5 Recent advances in gene transfer technology therefore open up exciting possibilities for efficient and safe genetic modification of autologous cells in this context.6 As potential therapeutic applications are being considered, attention has begun to be focused on issues of safety in the clinical arena. This has arisen in part from efforts to understand the biology of reprogramming as well as from an increasing capability to scrutinize the genome and epigenome at high resolution.
Published: 2011
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17. Trisomy 21 mid-trimester amniotic fluid induced pluripotent stem cells maintain genetic signatures during reprogramming: implications for disease modeling and cryobanking

Author: Assunta Pandolfi, Panicos Shangaris, Drew Ellershaw, Anna L. David, Jonathan J. Waters, Pascale V. Guillot, Paolo De Coppi, Sayandip Mukherjee, Adrian J. Thrasher, Agostino Pierro, Steven W. Shaw, Caterina Pipino, Michael P. Blundell, Marina Cavazzana, Peggy Sung, and Gustavo Mostoslavsky
Subjects: Cryopreservation, Induced Pluripotent Stem Cells, Amniotic stem cells, Cell Biology, Embryoid body, Biology, Amniotic Fluid, Embryonic stem cell, Models, Biological, Mice, SOX2, Pregnancy, Amniotic epithelial cells, Prenatal Diagnosis, Immunology, Cancer research, Animals, Humans, Female, Stem cell, Down Syndrome, Induced pluripotent stem cell, Reprogramming, Developmental Biology, Biotechnology
Abstract: Trisomy 21 is the most common chromosomal abnormality and is associated primarily with cardiovascular, hematological, and neurological complications. A robust patient-derived cellular model is necessary to investigate the pathophysiology of the syndrome because current animal models are limited and access to tissues from affected individuals is ethically challenging. We aimed to derive induced pluripotent stem cells (iPSCs) from trisomy 21 human mid-trimester amniotic fluid stem cells (AFSCs) and describe their hematopoietic and neurological characteristics. Human AFSCs collected from women undergoing prenatal diagnosis were selected for c-KIT(+) and transduced with a Cre-lox-inducible polycistronic lentiviral vector encoding SOX2, OCT4, KLF-4, and c-MYC (50,000 cells at a multiplicity of infection (MOI) 1-5 for 72 h). The embryonic stem cell (ESC)-like properties of the AFSC-derived iPSCs were established in vitro by embryoid body formation and in vivo by teratoma formation in RAG2(-/-), γ-chain(-/-), C2(-/-) immunodeficient mice. Reprogrammed cells retained their cytogenetic signatures and differentiated into specialized hematopoietic and neural precursors detected by morphological assessment, immunostaining, and RT-PCR. Additionally, the iPSCs expressed all pluripotency markers upon multiple rounds of freeze-thawing. These findings are important in establishing a patient-specific cellular platform of trisomy 21 to study the pathophysiology of the aneuploidy and for future drug discovery.
Published: 2014

18. High plasticity of pediatric adipose tissue-derived stem cells: too much for selective skeletogenic differentiation?

Author: Patrizia Ferretti, Georgios Kleftouris, Neil W. Bulstrode, Leonardo Guasti, Weerapong Prasongchean, Adrian J. Thrasher, and Sayandip Mukherjee
Subjects: Pathology, medicine.medical_specialty, Cellular differentiation, Neurogenesis, Blotting, Western, Adipose tissue, Biology, Real-Time Polymerase Chain Reaction, Immunoenzyme Techniques, Osteogenesis, medicine, Humans, RNA, Messenger, Induced pluripotent stem cell, Child, Original Articles and Reviews, Cells, Cultured, Stem cell transplantation for articular cartilage repair, Cell Proliferation, Reverse Transcriptase Polymerase Chain Reaction, Cartilage, Stem Cells, Cell Differentiation, Cell Biology, General Medicine, Chondrogenesis, Flow Cytometry, Cell biology, medicine.anatomical_structure, Adipose Tissue, Stem cell, Reprogramming, Biomarkers, Developmental Biology
Abstract: Stem cells derived from adipose tissue are a potentially important source for autologous cell therapy and disease modeling, given fat tissue accessibility and abundance. Critical to developing standard protocols for therapeutic use is a thorough understanding of their potential, and whether this is consistent among individuals, hence, could be generally inferred. Such information is still lacking, particularly in children. To address these issues, we have used different methods to establish stem cells from adipose tissue (adipose-derived stem cells [ADSCs], adipose explant dedifferentiated stem cells [AEDSCs]) from several pediatric patients and investigated their phenotype and differentiation potential using monolayer and micromass cultures. We have also addressed the overlooked issue of selective induction of cartilage differentiation. ADSCs/AEDSCs from different patients showed a remarkably similar behavior. Pluripotency markers were detected in these cells, consistent with ease of reprogramming to induced pluripotent stem cells. Significantly, most ADSCs expressed markers of tissue-specific commitment/differentiation, including skeletogenic and neural markers, while maintaining a proliferative, undifferentiated morphology. Exposure to chondrogenic, osteogenic, adipogenic, or neurogenic conditions resulted in morphological differentiation and tissue-specific marker upregulation. These findings suggest that the ADSC “lineage-mixed” phenotype underlies their significant plasticity, which is much higher than that of chondroblasts we studied in parallel. Finally, whereas selective ADSC osteogenic differentiation was observed, chondrogenic induction always resulted in both cartilage and bone formation when a commercial chondrogenic medium was used; however, chondrogenic induction with a transforming growth factor β1-containing medium selectively resulted in cartilage formation. This clearly indicates that careful simultaneous assessment of bone and cartilage differentiation is essential when bioengineering stem cell-derived cartilage for clinical intervention.
Published: 2012

19. Functional human artificial chromosomes are generated and stably maintained in human embryonic stem cells

Author: Zoia L. Monaco, Adrian J. Thrasher, Mohammed Yusuf, Sayandip Mukherjee, Emanuela V. Volpi, Daniela Moralli, Mohammad A. Mandegar, Suhail Khoja, William James, David Yiu Leung Chan, Michael P. Blundell, and Sally A. Cowley
Subjects: Neurons, Cell division, Cell growth, Fluorescent Antibody Technique, Cell Differentiation, Articles, Herpesvirus 1, Human, General Medicine, Human artificial chromosome, Biology, Amplicon, Flow Cytometry, Embryonic stem cell, Molecular biology, Chromosomes, Artificial, Human, Cell Line, Cell culture, Genetics, Humans, Stem cell, Molecular Biology, Gene, Embryonic Stem Cells, Genetics (clinical)
Abstract: We present a novel and efficient non-integrating gene expression system in human embryonic stem cells (hESc) utilizing human artificial chromosomes (HAC), which behave as autonomous endogenous host chromosomes and segregate correctly during cell division. HAC are important vectors for investigating the organization and structure of the kinetochore, and gene complementation. HAC have so far been obtained in immortalized or tumour-derived cell lines, but never in stem cells, thus limiting their potential therapeutic application. In this work, we modified the herpes simplex virus type 1 amplicon system for efficient transfer of HAC DNA into two hESc. The deriving stable clones generated green fluorescent protein gene-expressing HAC at high frequency, which were stably maintained without selection for 3 months. Importantly, no integration of the HAC DNA was observed in the hESc lines, compared with the fibrosarcoma-derived control cells, where the exogenous DNA frequently integrated in the host genome. The hESc retained pluripotency, differentiation and teratoma formation capabilities. This is the first report of successfully generating gene expressing de novo HAC in hESc, and is a significant step towards the genetic manipulation of stem cells and potential therapeutic applications.
Published: 2011

20. Emerging Neuronal Precursors from Amniotic Fluid–Derived Down Syndrome Induced Pluripotent Stem Cells

Author: Sayandip Mukherjee, Paolo DeCoppi, Adrian J. Thrasher, Anna L. David, and Caterina Pipino
Subjects: Down syndrome, Pathology, medicine.medical_specialty, Amniotic fluid, Induced Pluripotent Stem Cells, Cell Differentiation, Spinal muscular atrophy, Nestin, Biology, Amniotic Fluid, medicine.disease, Cell biology, Microscopy, Fluorescence, Neural Stem Cells, Genetics, medicine, Humans, Molecular Medicine, Down Syndrome, Progenitor cell, Induced pluripotent stem cell, Trisomy, Molecular Biology, Reprogramming
Abstract: bsenceofeffectiveandreliableanimaland cellularmodels for studying neurodevelopmental and neurode-generative disorders such as Parkinson’s disease, Alzhei-mer’s disease (AD), Huntington’s disease, amyotropic lateralsclerosis, spinal muscular atrophy, and many others has se-verely compromised both basic and translational research inthe arena of such complex disorders. However, recent ad-vancements in the ﬁeld of cellular reprogramming haveprovided an effective tool to study such disorders utilizingpatient-derived cells. Through ectopic overexpression of aFIG. 1. Immunophenotypic characterization of neuronal precursors and progenitors emerging out of trisomy 21 amnioticﬂuid–derived induced pluripotent stem cells (iPSCs). Nes, nestin; Tuj1, tubulin beta-III.
Published: 2014
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21. Lentivirus-mediated Reprogramming of Somatic Cells in the Absence of Transgenic Transcription Factors

Author: Sayandip Mukherjee, Nicole M. Kane, Joanne C. Mountford, Michael P. Blundell, Jenny A. Greig, Wai K. Lee, Adrian J. Thrasher, Manfred Schmidt, Andrew H. Baker, Christof von Kalle, Miles D. Houslay, Graeme Milligan, and Ali Nowrouzi
Subjects: Somatic cell, Transgene, Induced Pluripotent Stem Cells, Biology, 03 medical and health sciences, 0302 clinical medicine, microRNA, Gene expression, Drug Discovery, Genetics, Humans, Induced pluripotent stem cell, Transcription factor, Molecular Biology, 030304 developmental biology, Pharmacology, 0303 health sciences, Cell Differentiation, Cell biology, Gene expression profiling, Retroviridae, 030220 oncology & carcinogenesis, Molecular Medicine, Original Article, Reprogramming
Abstract: Retroviral vectors remain the most efficient and widely applied system for induction of pluripotency. However, mutagenic effects have been documented in both laboratory and clinical gene therapy studies, principally as a result of dysregulated host gene expression in the proximity of defined integration sites. Here, we report that cells with characteristics of pluripotent stem cells can be produced from normal human fibroblasts in the absence of reprogramming transcription factors (TFs) during lentiviral (LV) vector–mediated gene transfer. This occurred via induced alterations in host gene and microRNA (miRNA) expression and detrimental changes in karyotype. These findings demonstrate that vector-induced genotoxicity may alone play a role in somatic cell reprogramming derivation and urges caution when using integrating vectors in this setting. Clearer understanding of this process may additionally reveal novel insights into reprogramming pathways.
Published: 2010

22. Nonintegrating lentivector vaccines stimulate prolonged T-cell and antibody responses and are effective in tumor therapy

Author: L Apolonia, Gerben Bouma, Mary Collins, David Escors, Michael P. Blundell, Sayandip Mukherjee, Adrian J. Thrasher, and Katarzyna Karwacz
Subjects: Cellular immunity, Antibodies, Neoplasm, T cell, T-Lymphocytes, Virus Integration, Immunology, Antigen presentation, Genetic Vectors, Mice, Transgenic, Antibodies, Viral, Microbiology, Cancer Vaccines, Viral vector, Mice, Immune system, Antigen, Virology, Neoplasms, Vaccines and Antiviral Agents, medicine, Animals, Hepatitis B Vaccines, Mice, Inbred BALB C, biology, Lentivirus, medicine.anatomical_structure, Insect Science, Humoral immunity, biology.protein, Antibody
Abstract: Lentiviral vectors (lentivectors) are effective for stimulation of cell-mediated and humoral immunity following subcutaneous and intramuscular immunization. However, lentivector genome integration carries a risk of perturbation of host gene expression. Here, we demonstrate that lentivectors with multiple mutations that prevent integration are also effective immunogens. First, systemic CD8 + T-cell responses to the model antigen ovalbumin were detected following subcutaneous injection of nonintegrating lentivectors. Transfer of transgenic OT1 T cells demonstrated that antigen presentation persisted for at least 30 days. Furthermore, an enhanced CD8 + T-cell response, peaking at 7 days, was stimulated by coexpression of p38 MAP kinase or an NF-κB activator from the same vector. Second, we demonstrated systemic CD8 + T-cell and antibody responses to the secreted hepatitis B virus (HBV) surface antigen expressed from a nonintegrating lentivector injected intramuscularly. The induction, specificity, and kinetics of antibody production closely mimicked those of natural HBV infection. In this case, both the vector genome and the immune response were maintained for at least 2 months. Together, our data indicate that nonintegrating lentivectors can be employed to generate effective vaccines.
Published: 2009

23. Induced Pluripotent Stem Cells: a New Hope or a New Controversy?

Author: Sayandip Mukherjee
Subjects: Somatic cell, stem cells, therapeutic cloning, Cellular differentiation, Genetics, Nerve Impulses, Biology, Stem cell, Induced pluripotent stem cell, Neuroscience, Organism, Genealogy
Abstract: It seems unbelievable but it is true – cells within an organism are genetically almost identical and yet they are as dissimilar structurally and functionally as the human mind can conceive. The neurons which conduct the nerve impulses, the villi which line the gastrointestinal tract, the retinal cells which are responsible for our vision, and the immune cells which act as the body’s sentinel have hardly anything in common between them. All these highly specialized cells are said to be terminally differentiated - they have lost their ability to become something else. Therefore, it was heralded as a significant breakthrough in science, when more than a decade ago, Ian Wilmut and colleagues at the Roslin Institute in Scotland demonstrated that a mature differentiated somatic cell taken from an adult mammal could be reprogrammed to give rise to an entire animal, which came to be known to the entire world as Dolly the sheep (Campbell 1996, 64).
Published: 2008
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24. Proviral Progeny of Heterodimeric Virions Reveal a High Crossover Rate for Human Immunodeficiency Virus Type 2▿

Author: Joseph P. Dougherty, Hui-Ling Rose Lee, Sayandip Mukherjee, and Yacov Ron
Subjects: Immunology, Genetic Vectors, Biology, Microbiology, Virus, Chromosomal crossover, law.invention, Evolution, Molecular, Proviruses, law, Virology, Murine leukemia virus, Crossing Over, Genetic, Genetics, Models, Genetic, Virion, virus diseases, Provirus, biology.organism_classification, Genetic Diversity and Evolution, Insect Science, Viral evolution, Lentivirus, HIV-2, Recombinant DNA, Recombination
Abstract: Human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS in humans, exhibits a very high rate of recombination. Bearing in mind the significant epidemiological and clinical contrast between HIV-2 and HIV-1 as well as the critical role that recombination plays in viral evolution, we examined the nature of HIV-2 recombination. Towards this end, a strategy was devised to measure the rate of crossover of HIV-2 by evaluating recombinant progeny produced exclusively by heterodimeric virions. The results showed that HIV-2 exhibits a crossover rate similar to that of HIV-1 and murine leukemia virus, indicating that the extremely high rate of crossover is a common retroviral feature.
Published: 2006

25. A HIV-2-based self-inactivating vector for enhanced gene transduction

Author: Joseph P. Dougherty, Hui-Ling Rose Lee, Sayandip Mukherjee, Annmarie L. Pacchia, and Yacov Ron
Subjects: Genetic Vectors, Bioengineering, Biology, Applied Microbiology and Biotechnology, Virus, Cell Line, Transduction (genetics), Plasmid, Transduction, Genetic, Cell Line, Tumor, Animals, Humans, Cloning, Molecular, Promoter Regions, Genetic, Gene, Cells, Cultured, HIV Long Terminal Repeat, Genetic transfer, General Medicine, Virology, Rats, Titer, Cell culture, HIV-2, Gene Deletion, Biotechnology, Plasmids
Abstract: The employment of HIV-1-based vectors in clinical trials is controversial mainly due to the lethal nature of the virus. HIV-2 is less pathogenic in nature and therefore is likely to be safer for vector design and production. We developed HIV-2-based self-inactivating vectors in which 520 bp out of 554 bp of the viral U3 was deleted. Interestingly, high titers were obtained only when an exogenous promoter was used to drive expression of viral RNA. It was found that the vectors could target a wide range of mammalian cell types including primary neuronal cells and could yield long term expression. It is also noteworthy that the HIV-2 vectors could be effectively cross-packaged into HIV-1 core, which might provide for enhanced safety by reducing the recombination potential of the system.
Published: 2006

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25 results on '"Sayandip Mukherjee"'

1. Chemical inactivation of two non-enveloped viruses results in distinct thermal unfolding patterns and morphological alterations

2. Development of a pseudo-typed virus particle based method to determine the efficacy of virucidal agents

3. SG-APSIC1050: Personal care formulations prove effective against evolving variants of SARS-CoV-2: Implications for public health and hygiene

4. Personal care formulations demonstrate virucidal efficacy against multiple SARS-CoV-2 variants of concern: Implications for hand hygiene and public health

5. Generation of functional neutrophils from a mouse model of X-linked chronic granulomatous disorder using induced pluripotent stem cells.

6. Antiviral efficacy of personal care formulations against Severe Acute Respiratory Syndrome Coronavirus 2

7. CPC-containing oral rinses inactivate SARS-CoV-2 variants and are active in the presence of human saliva

8. Personal care formulations demonstrate virucidal efficacy against multiple SARS-CoV-2 variants of concern: implications for hand hygiene

9. Virucidal activity of CPC-containing oral rinses against SARS-CoV-2 variants and are active in the presence of human saliva

10. Study of J/ψ meson production inside jets in pp collisions at s=8TeV

11. Gene therapy for PIDs: Progress, pitfalls and prospects

12. Brief Report: Self-Organizing Neuroepithelium from Human Pluripotent Stem Cells Facilitates Derivation of Photoreceptors

13. Valproic Acid Confers Functional Pluripotency to Human Amniotic Fluid Stem Cells in a Transgene-free Approach

14. Progress and Prospects: Advancements in Retroviral Vector Design, Generation, and Application

15. High Rate of Genetic Recombination in Murine Leukemia Virus: Implications for Influencing Proviral Ploidy

16. iPSCs: Unstable Origins?

17. Trisomy 21 mid-trimester amniotic fluid induced pluripotent stem cells maintain genetic signatures during reprogramming: implications for disease modeling and cryobanking

18. High plasticity of pediatric adipose tissue-derived stem cells: too much for selective skeletogenic differentiation?

19. Functional human artificial chromosomes are generated and stably maintained in human embryonic stem cells

20. Emerging Neuronal Precursors from Amniotic Fluid–Derived Down Syndrome Induced Pluripotent Stem Cells

21. Lentivirus-mediated Reprogramming of Somatic Cells in the Absence of Transgenic Transcription Factors

22. Nonintegrating lentivector vaccines stimulate prolonged T-cell and antibody responses and are effective in tumor therapy

23. Induced Pluripotent Stem Cells: a New Hope or a New Controversy?

24. Proviral Progeny of Heterodimeric Virions Reveal a High Crossover Rate for Human Immunodeficiency Virus Type 2▿

25. A HIV-2-based self-inactivating vector for enhanced gene transduction

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