Potential applications of genome editing in anti-HIV therapy. Site-specific DNA breaks created by engineered nucleases can be repaired by error-prone NHEJ or, if a homologous DNA repair template is also present, by more precise HDR pathways. NHEJ frequently results in indels, allowing disruption of genes such as the HIV-1 coreceptors CCR5 and CXCR4 or integrated HIV-1 genomes. HDR could be used to introduce small mutations into host restriction factors to restore anti-HIV activities or into host dependency factors to limit their use by the virus. Alternatively, HDR could be used to site-specifically insert anti-HIV genes at the site of the DNA break, including at a disrupted CCR5 locus.