7 results on '"Fangzhi Tan"'
Search Results
2. AAV-ie-K558R mediated cochlear gene therapy and hair cell regeneration
- Author
-
Yong Tao, Xiaoyi Liu, Liu Yang, Cenfeng Chu, Fangzhi Tan, Zehua Yu, Junzi Ke, Xiang Li, Xiaofei Zheng, Xingle Zhao, Jieyu Qi, Chao-Po Lin, Renjie Chai, Guisheng Zhong, and Hao Wu
- Subjects
Medicine ,Biology (General) ,QH301-705.5 - Abstract
Abstract The cochlea consists of multiple types of cells, including hair cells, supporting cells and spiral ganglion neurons, and is responsible for converting mechanical forces into electric signals that enable hearing. Genetic and environmental factors can result in dysfunctions of cochlear and auditory systems. In recent years, gene therapy has emerged as a promising treatment in animal deafness models. One major challenge of the gene therapy for deafness is to effectively deliver genes to specific cells of cochleae. Here, we screened and identified an AAV-ie mutant, AAV-ie-K558R, that transduces hair cells and supporting cells in the cochleae of neonatal mice with high efficiency. AAV-ie-K558R is a safe vector with no obvious deficits in the hearing system. We found that AAV-ie-K558R can partially restore the hearing loss in Prestin KO mice and, importantly, deliver Atoh1 into cochlear supporting cells to generate hair cell-like cells. Our results demonstrate the clinical potential of AAV-ie-K558R for treating the hearing loss caused by hair cell death.
- Published
- 2022
- Full Text
- View/download PDF
3. Organized cannabinoid receptor distribution in neurons revealed by super-resolution fluorescence imaging
- Author
-
Jie Yang, Shanshan Li, Simeng Zhao, Tong Wang, Min Diao, Cuiping Tian, Zhi-Jie Liu, Fangzhi Tan, Tian Hua, Garth John Thompson, Ying Zhang, Chao-Po Lin, Dylan Deska-Gauthier, Wenqing Shui, Guisheng Zhong, Ya Qin, Hui Li, and Quan Wang
- Subjects
Male ,0301 basic medicine ,Agonist ,Fluorescence-lifetime imaging microscopy ,Cannabinoid receptor ,medicine.drug_class ,medicine.medical_treatment ,Science ,General Physics and Astronomy ,Article ,General Biochemistry, Genetics and Molecular Biology ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Receptor, Cannabinoid, CB1 ,medicine ,Animals ,Super-resolution microscopy ,Receptor ,lcsh:Science ,Cells, Cultured ,Cytoskeleton ,G protein-coupled receptor ,Mice, Knockout ,Neurons ,Multidisciplinary ,Chemistry ,musculoskeletal, neural, and ocular physiology ,Brain ,Fluorescence recovery after photobleaching ,food and beverages ,General Chemistry ,Cellular neuroscience ,Axons ,Molecular Imaging ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,Microscopy, Fluorescence ,nervous system ,Female ,lcsh:Q ,lipids (amino acids, peptides, and proteins) ,Cannabinoid ,psychological phenomena and processes ,030217 neurology & neurosurgery ,Intracellular ,Fluorescence Recovery After Photobleaching - Abstract
G-protein-coupled receptors (GPCRs) play important roles in cellular functions. However, their intracellular organization is largely unknown. Through investigation of the cannabinoid receptor 1 (CB1), we discovered periodically repeating clusters of CB1 hotspots within the axons of neurons. We observed these CB1 hotspots interact with the membrane-associated periodic skeleton (MPS) forming a complex crucial in the regulation of CB1 signaling. Furthermore, we found that CB1 hotspot periodicity increased upon CB1 agonist application, and these activated CB1 displayed less dynamic movement compared to non-activated CB1. Our results suggest that CB1 forms periodic hotspots organized by the MPS as a mechanism to increase signaling efficacy upon activation., Despite the importance of G-protein-coupled receptors in many cellular functions, their intracellular organisation is largely unknown. The authors identified periodically repeating clusters of cannabinoid receptor 1 hotspots within neuronal axons that are dynamically regulated by CB1 agonists.
- Published
- 2020
4. An AAV-ie based Vaccine effectively protects against SARS-CoV-2 and Circulating Variants
- Author
-
Chao-bo Lin, Fangzhi Tan, Haopeng Wang, Junzi Ke, Jie Yang, Guisheng Zhong, and Simeng Zhao
- Subjects
Immunogen ,Coronavirus disease 2019 (COVID-19) ,biology ,business.industry ,viruses ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immune sera ,Virology ,Vaccination ,Pandemic ,biology.protein ,Medicine ,Vector (molecular biology) ,Antibody ,business - Abstract
Prophylactic vaccines against SARS-CoV-2 have been extensively developed globally to overcome the COVID-19 pandemic. However, recently emerging SARS-CoV-2 variants B.1.1.7 and B.1.351 limit the vaccine protection effects and successfully escape antibody cocktail treatment. Herein, based on our previously engineered adeno-associated viral (AAV) vector, AAV-ie, and systematic immunogen screening, we developed an AAV-ie-S1 vaccine with thermostability, high efficiency, safety, and single-dose vaccination advantage. Importantly, the AAV-ie-S1 immune sera efficiently neutralize B.1.1.7 and B.1.351, indicating a potential to circumvent the spreading of SARS-CoV-2.
- Published
- 2021
5. Organized cannabinoid receptor distribution in neurons revealed by super-resolution fluorescence imaging
- Author
-
Quan Wang, Zhi-Jie Liu, Tian Hua, Wenqing Shui, Guisheng Zhong, Min Diao, Tian Cuiping, Garth John Thompson, Chao-Po Lin, Simeng Zhao, Jie Yang, Fangzhi Tan, Hui Li, Tong Wang, Shanshan Li, Dylan Deska-Gauthier, and Ying Zhang
- Subjects
Agonist ,Fluorescence-lifetime imaging microscopy ,congenital, hereditary, and neonatal diseases and abnormalities ,Cannabinoid receptor ,medicine.drug_class ,Chemistry ,food and beverages ,CANNABINOID RECEPTOR 1 ,Superresolution ,Cell biology ,medicine ,Receptor ,Intracellular ,G protein-coupled receptor - Abstract
G-protein-coupled receptors (GPCRs) play important roles in cellular functions. However, their intracellular organization is largely unknown. Through investigation of the cannabinoid receptor 1 (CB1), we discovered periodically repeating clusters of CB1 hotspots within the axons of neurons. We observed these CB1 hotspots interact with the membrane-associated periodic skeleton (MPS) forming a complex crucial in the regulation of CB1 signaling. Furthermore, we found that CB1 hotspot periodicity increased upon CB1 agonist application, and these activated CB1 displayed less dynamic movement compared to non-activated CB1. Our results suggest that CB1 forms periodic hotspots organized by the MPS as a mechanism to increase signaling efficacy when being activated.
- Published
- 2020
- Full Text
- View/download PDF
6. AAV-ie enables safe and efficient gene transfer to inner ear cells
- Author
-
Cenfeng Chu, Shuijin He, Fangzhi Tan, Dan You, Cheng Cheng, Wenyan Li, Bing Su, Yunbo Qiao, Jieyu Qi, Weidong Zhao, Chao Zhong, Renjie Chai, Guisheng Zhong, Huawei Li, Ke Li, Xiaoyi Liu, and Xin Chen
- Subjects
0301 basic medicine ,Male ,Hearing loss ,Genetic enhancement ,Science ,viruses ,Genetic Vectors ,General Physics and Astronomy ,ATOH1 Gene ,02 engineering and technology ,Gene delivery ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Virus ,Article ,03 medical and health sciences ,Mice ,medicine ,otorhinolaryngologic diseases ,Basic Helix-Loop-Helix Transcription Factors ,Animals ,Inner ear ,lcsh:Science ,Hearing Loss ,Cochlea ,Cells, Cultured ,Multidisciplinary ,Hair Cells, Auditory, Inner ,Regeneration (biology) ,Gene Transfer Techniques ,General Chemistry ,Genetic Therapy ,Dependovirus ,021001 nanoscience & nanotechnology ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Q ,Female ,sense organs ,medicine.symptom ,0210 nano-technology - Abstract
Hearing loss is the most common sensory disorder. While gene therapy has emerged as a promising treatment of inherited diseases like hearing loss, it is dependent on the identification of gene delivery vectors. Adeno-associated virus (AAV) vector-mediated gene therapy has been approved in the US for treating a rare inherited eye disease but no safe and efficient vectors have been identified that can target the diverse types of inner ear cells. Here, we identify an AAV variant, AAV-inner ear (AAV-ie), for gene delivery in mouse inner ear. Our results show that AAV-ie transduces the cochlear supporting cells (SCs) with high efficiency, representing a vast improvement over conventional AAV serotypes. Furthermore, after AAV-ie-mediated transfer of the Atoh1 gene, we find that many SCs trans-differentiated into new HCs. Our results suggest that AAV-ie is a useful tool for the cochlear gene therapy and for investigating the mechanism of HC regeneration., There are currently few AAV vectors that can effectively target the diverse cell types of the inner ear. Here the authors design AAV-ie for gene delivery to the mouse cochlea, targeting cochlear supporting cells.
- Published
- 2019
7. TGFβ signaling hyperactivation-induced tumorigenicity during the derivation of neural progenitors from mouse ESCs
- Author
-
Ran Wang, Guoqing Cai, Xiongjun Wang, Yun Qian, Yunbo Qiao, Naihe Jing, Xianfa Yang, Su Feng, Ke Tang, Xingxu Huang, Fangzhi Tan, and Kun Chen
- Subjects
0301 basic medicine ,Carcinogenesis ,medicine.medical_treatment ,Cellular differentiation ,Biology ,Cell Line ,Epigenesis, Genetic ,03 medical and health sciences ,Mice ,Neural Stem Cells ,Transforming Growth Factor beta ,TGF beta signaling pathway ,Genetics ,medicine ,Animals ,Progenitor cell ,Induced pluripotent stem cell ,Molecular Biology ,reproductive and urinary physiology ,urogenital system ,Cell Differentiation ,Mouse Embryonic Stem Cells ,Cell Biology ,General Medicine ,Stem-cell therapy ,Embryonic stem cell ,Neural stem cell ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,embryonic structures ,biological phenomena, cell phenomena, and immunity ,Transcriptome ,Germ cell ,Signal Transduction - Abstract
Clinical therapies of pluripotent stem cells (PSCs)-based transplantation have been hindered by frequent development of teratomas or tumors in animal models and clinical patients. Therefore, clarifying the mechanism of carcinogenesis in stem cell therapy is of great importance for reducing the risk of tumorigenicity. Here we differentiate Oct4-GFP mouse embryonic stem cells (mESCs) into neural progenitor cells (NPCs) and find that a minority of Oct4+ cells are continuously sustained at Oct4+ state. These cells can be enriched and proliferated in a standard ESC medium. Interestingly, the differentiation potential of these enriched cells is tightly restricted with much higher tumorigenic activity, which are thus defined as differentiation-resistant ESCs (DR-ESCs). Transcriptomic and epigenomic analyses show that DR-ESCs are characterized by primordial germ cell-like gene signatures (Dazl, Rec8, Stra8, Blimp1, etc.) and specific epigenetic patterns distinct from mESCs. Moreover, the DR-ESCs possess germ cell potential to generate Sycp3+ haploid cells and are able to reside in sperm-free spermaduct induced by busulfan. Finally, we find that TGFβ signaling is overactivated in DR-ESCs, and inhibition of TGFβ signaling eliminates the tumorigenicity of mESC-derived NPCs by inducing the full differentiation of DR-ESCs. These data demonstrate that these TGFβ-hyperactivated germ cell-like DR-ESCs are the main contributor for the tumorigenicity of ESCs-derived target cell therapy and that inhibition of TGFβ signaling in ESC-derived NPC transplantation could drastically reduce the risk of tumor development.
- Published
- 2017
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.