The discovery and development of RNA-based therapies for treatment of HIV-1 infection

Introduction Long-term control of HIV-1 infection can potentially be achieved using autologous stem cell transplants with gene-modified cells. Non-coding RNAs represent a diverse class of therapeutic agents including ribozymes, RNA aptamers and decoys, small interfering RNAs, short hairpin RNAs, and U1 interference RNAs that can be designed to inhibit HIV-1 replication. They have been engineered for delivery as drugs to complement current HIV-1 therapies and as gene therapies for a potential HIV-1 functional cure. Areas covered This review surveys the past three decades of development of these RNA technologies with a focus on their efficacy and safety for treating HIV-1 infections. We describe the mechanisms of each RNA-based agent, targets they have been developed against, efforts to enhance their stability and efficacy, and we evaluate their performance in past and ongoing preclinical and clinical trials. Expert opinion RNA-based technologies are among the top candidates for gene therapies where they can be stably expressed for long-term suppression of HIV-1. Advances in both gene and drug delivery strategies and improvements to non-coding RNA stability and antiviral properties will cooperatively drive forward progress in improving drug therapy and engineering HIV-1 resistant cells.