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2 results on '"Manjunath N Manjunath"'

1. CCR5 Gene Editing of Resting CD4+ T Cells by Transient ZFN Expression From HIV Envelope Pseudotyped Nonintegrating Lentivirus Confers HIV-1 Resistance in Humanized Mice

Author

Guohua Yi, Jang Gi Choi, Preeti Bharaj, Sojan Abraham, Ying Dang, Tal Kafri, Ogechika Alozie, Manjunath N Manjunath, and Premlata Shankar

Subjects
CCR5 gene editing, HIV-1 therapy, humanized mice, non-integrating lentivirus, resting CD4+ T cells, zinc finger nucleases, Therapeutics. Pharmacology, RM1-950
Abstract

CCR5 disruption by zinc finger nucleases (ZFNs) is a promising method for HIV-1 gene therapy. However, successful clinical translation of this strategy necessitates the development of a safe and effective method for delivery into relevant cells. We used non-integrating lentivirus (NILV) for transient expression of ZFNs and pseudotyped the virus with HIV-envelope for targeted delivery to CD4+ T cells. Both activated and resting primary CD4+ T cells transduced with CCR5-ZFNs NILV showed resistance to HIV-1 infection in vitro. Furthermore, NILV transduced resting CD4+ T cells from HIV-1 seronegative individuals were resistant to HIV-1 challenge when reconstituted into NOD-scid IL2rγc null (NSG) mice. Likewise, endogenous virus replication was suppressed in NSG mice reconstituted with CCR5-ZFN–transduced resting CD4+ T cells from treatment naïve as well as ART-treated HIV-1 seropositive patients. Taken together, NILV pseudotyped with HIV envelope provides a simple and clinically viable strategy for HIV-1 gene therapy.

Published
2014
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2. CCR5 Gene Editing of Resting CD4+ T Cells by Transient ZFN Expression From HIV Envelope Pseudotyped Nonintegrating Lentivirus Confers HIV-1 Resistance in Humanized Mice

Author

Manjunath N Manjunath, Preeti Bharaj, Jang-Gi Choi, Sojan Abraham, Guohua Yi, Premlata Shankar, Ogechika Alozie, Ying Dang, and Tal Kafri

Subjects
Genetic enhancement, Endogenous retrovirus, non-integrating lentivirus, Virus, 03 medical and health sciences, 0302 clinical medicine, Genome editing, Drug Discovery, zinc finger nucleases, 030304 developmental biology, 0303 health sciences, biology, CCR5 gene editing, lcsh:RM1-950, virus diseases, Translation (biology), biology.organism_classification, Virology, Zinc finger nuclease, In vitro, resting CD4+ T cells, 3. Good health, HIV-1 therapy, humanized mice, lcsh:Therapeutics. Pharmacology, 030220 oncology & carcinogenesis, Lentivirus, Molecular Medicine, Original Article
Abstract

CCR5 disruption by zinc finger nucleases (ZFNs) is a promising method for HIV-1 gene therapy. However, successful clinical translation of this strategy necessitates the development of a safe and effective method for delivery into relevant cells. We used non-integrating lentivirus (NILV) for transient expression of ZFNs and pseudotyped the virus with HIV-envelope for targeted delivery to CD4(+) T cells. Both activated and resting primary CD4(+) T cells transduced with CCR5-ZFNs NILV showed resistance to HIV-1 infection in vitro. Furthermore, NILV transduced resting CD4(+) T cells from HIV-1 seronegative individuals were resistant to HIV-1 challenge when reconstituted into NOD-scid IL2rγc null (NSG) mice. Likewise, endogenous virus replication was suppressed in NSG mice reconstituted with CCR5-ZFN-transduced resting CD4(+) T cells from treatment naïve as well as ART-treated HIV-1 seropositive patients. Taken together, NILV pseudotyped with HIV envelope provides a simple and clinically viable strategy for HIV-1 gene therapy.

Published
2014

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