CRISPR/Cas9-Derived Mutations Both Inhibit HIV-1 Replication and Accelerate Viral Escape

• DOI: 10.1016/j.celrep.2016.03.042
• Publication Date: 2016-04-09T21:33:07Z
• Authors: Zhen Wang; Qinghua Pan; Patrick Gendron; Weijun Zhu; Fei Guo; Shan Cen; Mark A. Wainberg; Chen Liang
• Keywords: Subgenomic mRNA; Indel; Guide RNA

Cas9 cleaves specific DNA sequences with the assistance of a programmable single guide RNA (sgRNA). Repairing this broken by cell's error-prone non-homologous end joining (NHEJ) machinery leads to insertions and deletions (indels) that often impair function. Using HIV-1, we have now demonstrated many these indels are indeed lethal for virus, but others lead emergence replication competent viruses resistant Cas9/sgRNA. This unexpected contribution development viral resistance is facilitated some not deleterious replication, refractory recognition same sgRNA as result changing target sequences. observation illustrates two opposite outcomes Cas9/sgRNA action, i.e., inactivation HIV-1 acceleration escape, thereby potentially limiting use in therapy.