1. 758. Towards Gene Knock out Therapy for AIDS/HIV: Targeted Disruption of CCR5 Using Engineered Zinc Finger Protein Nucleases (ZFNs)
- Author
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Kenneth Kim, Dmitry Guschin, Jeffrey C. Miller, Olga Liu, James L. Riley, Elena E. Perez, Edward J. Rebar, Carl H. June, Philip D. Gregory, Ya-Li Lee, Jianbin Wang, Dale Ando, Yann Jouvenot, Victor Bartsevich, and Michael C. Holmes
- Subjects
Zinc finger ,Genetics ,Pharmacology ,DNA repair ,fungi ,virus diseases ,Biology ,DNA repair protein XRCC4 ,Zinc finger nuclease ,Cell biology ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,Molecular Medicine ,Human genome ,Gene ,Molecular Biology ,Gene knockout ,DNA - Abstract
HIV entry into target cells requires binding of the envelope protein GP120 to the CD4 co-receptors CCR5 or CXCR4. Loss of these HIV co-receptors is therefore attractive as a potential therapy for HIV patients, yet no current methods permit the efficient therapeutic disruption of a chosen gene in the human genome. To this end, we have developed designed zinc-finger protein nucleases (ZFNs) to target predetermined sequences within the CCR5 gene. Once these ZFNs create a double strand break (DSB) in the targeted DNA, natural DNA repair pathways, including Non-Homologous End Joining (NHEJ), subsequently repair the DSB. Importantly, however, NHEJ is error prone and thus can result in permanent disruption of the targeted gene.
- Published
- 2006
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