Pathways Toward a Functional HIV-1 Cure: Balancing Promise and Perils of CRISPR Therapy

First identified as a viral defense mechanism, clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) has been transformed into a gene-editing tool. It now affords promise in the treatment and potential eradication of a range of divergent genetic, cancer, infectious, and degenerative diseases. Adapting CRISPR-Cas into a programmable endonuclease directed guide RNA (gRNA) has attracted international attention. It was recently awarded the 2020 Nobel Prize in Chemistry. The limitations of this technology have also been identified and work has been made in providing potential remedies. For treatment of the human immunodeficiency virus type one (HIV-1), in particular, a CRISPR-Cas9 approach was adapted to target then eliminate latent proviral DNA. To this end, we reviewed the promise and perils of CRISPR-Cas gene-editing strategies for HIV-1 elimination. Obstacles include precise delivery to reservoir tissue and cell sites of latent HIV-1 as well as assay sensitivity and specificity. The detection and consequent excision of common viral strain sequences and the avoidance of off-target activity will serve to facilitate a final goal of HIV-1 DNA elimination and accelerate testing in infected animals ultimately for use in man.