A comparative review on innovative gene therapy approaches for the treatment of HIV infection

Abstract

The worldwide burden of HIV continues to be a critical public health issue, although there has been considerable progress in antiretroviral therapy (ART). Lifelong treatment is needed because ART suppresses viral replication but not latent reservoirs. Gene therapy is being considered to be a very promising approach to address this issue by targeting host factors, enhancing the immune system resistance, or even directly removing the pro-viral DNA. This review explores the latest gene therapy approaches for HIV, including zinc-finger nucleases, TALENs, and CRISPR-Cas systems. Also, the review discusses biological mechanisms, preclinical and clinical validations, and therapeutic targets, for example, CCR5 disruption and pro-viral excision, delivery issues, off-target effects, and immunogenicity. Here, ZFNs are clinically most validated (first human data, CCR5 focus), TALENs are most precise but unproven in clinical studies, and CRISPR is most flexible and fastest moving in human studies. While there is still no cure for HIV, the chances of achieving and maintaining a drug-free treatment are improving all the time because of advancements in gene editing technology and delivery systems. This review concludes that CRISPR-Cas9 is currently the most promising gene-editing strategy for HIV treatment due to its ease of programming, ability to target multiple sites, and active research and development of next-level gene therapy approaches to cure HIV.