CRISPR-Cas13 RNA-Targeting Therapeutics for Achieving Functional HIV Remission in ReservoirContaining Tissues
TL;DR
Emerging findings indicated that Cas13-based constructs can efficiently reduce HIV RNA levels and blunt viral gene expression, though durable impacts on reservoir size and clinical remission remain to be demonstrated.
Abstract
Human immunodeficiency virus (HIV) persisted as a significant global health burden, with an estimated 40.8 million people living with HIV as of 2024 despite widespread access to combination antiretroviral therapy (cART). Lifelong therapy was still required because replication-competent provirus and low-level viral transcription persisted in long-lived reservoir-containing tissues, including lymphoid organs, gut-associated lymphoid tissue, and central nervous system niches. CRISPR-Cas13, a type VI RNA-guided nuclease, has emerged as a versatile platform for programmable RNA targeting, offering the possibility of selectively degrading HIV RNA transcripts while sparing the host genome. This narrative review examined CRISPR-Cas13 RNA-targeting therapeutics in the context of achieving functional HIV remission, synthesizing current knowledge on Cas13 biology, HIV reservoir dynamics, proof-of-concept studies, and translational delivery strategies to reservoir-rich tissues. A narrative review methodology was employed, drawing on peer-reviewed literature from PubMed, Scopus, and major publishers between 2015 and 2026, with emphasis on mechanistic and preclinical studies. Emerging findings indicated that Cas13-based constructs can efficiently reduce HIV RNA levels and blunt viral gene expression, though durable impacts on reservoir size and clinical remission remain to be demonstrated. Key limitations included delivery barriers, off-target and collateral RNA cleavage, immune recognition, and scalability in diverse patient populations. CRISPR-Cas13 RNA-targeting therapeutics represented a scientifically compelling avenue for shifting HIV management from lifelong suppression to functional remission, but substantial optimization of vector design, delivery to tissue reservoirs, and long-term safety is still required before clinical translation is realistic. Keywords: CRISPR-Cas13, RNA targeting, HIV reservoirs, Functional remission, Gene therapy.