Genome editing strategies potential tools for era

Authors: Kamel Khalili Rafal Kaminski Jennifer Gordon Laura Cosentino Wenhui Hu

Publish Date: 2015/02/26

Volume: 21, Issue: 3, Pages: 310-321

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Abstract

Current therapy for controlling human immunodeficiency virus HIV1 infection and preventing acquired immunodeficiency syndrome AIDS progression has profoundly decreased viral replication in cells susceptible to HIV1 infection but it does not eliminate the low level of viral replication in latently infected cells which contain integrated copies of HIV1 proviral DNA There is an urgent need for the development of HIV1 genome eradication strategies that will lead to a permanent or “sterile” cure of HIV1/AIDS In the past few years novel nucleaseinitiated genome editing tools have been developing rapidly including zinc finger nucleases ZFNs transcription activatorlike effector nucleases TALENs and the CRISPR/Cas9 system These surgical knives which can excise any genome provide a great opportunity to eradicate the HIV1 genome by targeting highly conserved regions of the HIV1 long terminal repeats or essential viral genes Given the time consuming and costly engineering of targetspecific ZFNs and TALENs the RNAguided endonuclease Cas9 technology has emerged as a simpler and more versatile technology to allow permanent removal of integrated HIV1 proviral DNA in eukaryotic cells and hopefully animal models or human patients The major unmet challenges of this approach at present include inefficient nuclease gene delivery potential offtarget cleavage and cellspecific genome targeting Nanoparticle or lentivirusmediated delivery of next generation Cas9 technologies including nickase or RNAguided FokI nuclease RFN will further improve the potential for genome editing to become a promising approach for curing HIV1/AIDS

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