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
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2014
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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.
| Reference Key |
yi2014molecularccr5
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|---|---|
| Authors | ;Guohua Yi;Jang Gi Choi;Preeti Bharaj;Sojan Abraham;Ying Dang;Tal Kafri;Ogechika Alozie;Manjunath N Manjunath;Premlata Shankar |
| Journal | coordination chemistry reviews |
| Year | 2014 |
| DOI |
10.1038/mtna.2014.52
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| URL | |
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