We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Zinc-finger Nuclease Editing of Human cxcr4 Promotes HIV-1 CD4<sup>+</sup> T Cell Resistance and Enrichment.
- Authors
Yuan, Jinyun; Wang, Jianbin; Crain, Karen; Fearns, Colleen; Kim, Kenneth A; Hua, Kevin L; Gregory, Philip D; Holmes, Michael C; Torbett, Bruce E
- Abstract
HIV-1-infected individuals can harbor viral isolates that can use CCR5, as well as CXCR4, for viral entry. To genetically engineer HIV-1 resistance in CD4+ T cells, we assessed whether transient, adenovirus delivered zinc-finger nuclease (ZFN) disruption of genomic cxcr4 or stable lentiviral expression of short hairpin RNAs (shRNAs) targeting CXCR4 mRNAs provides durable resistance to HIV-1 challenge. ZFN-modification of cxcr4 in CD4+ T cells was found to be superior to cell integrated lentivirus-expressing CXCR4 targeting shRNAs when CD4+ T cells were challenged with HIV-1s that utilizes CXCR4 for entry. Cxcr4 disruption in CD4+ T cells was found to be stable, conferred resistance, and provided for continued cell enrichment during HIV-1 infection in tissue culture and, in vivo, in peripheral blood mononuclear cell transplanted NSG mice. Moreover, HIV-1-infected mice with engrafted cxcr4 ZFN-modified CD4+ T cells demonstrated lower viral levels in contrast to mice engrafted with unmodified CD4+ T cells. These findings provide evidence that ZFN-mediated disruption of cxcr4 provides a selective advantage to CD4+ T cells during HIV-1 infection.
- Subjects
HIV infections; T cells; ZINC; NUCLEASES; LABORATORY mice
- Publication
Molecular Therapy, 2012, Vol 20, Issue 4, p849
- ISSN
1525-0016
- Publication type
Art Reproduction
- DOI
10.1038/mt.2011.310