The discovery and development of RNA-based therapies for treatment of HIV-1 infection. (1st February 2023)

• Record Type: Journal Article
• Authors: Chen, Michelle J; Gatignol, Anne; Scarborough, Robert J.
• Is Part Of: Expert opinion on drug discovery. Volume 18:Number 2(2023)
• Page Start: 163
• Page End: 179
• Publication Date: 2023-02-01
• Subjects: Aptamer -- Human Immunodeficiency Virus -- ribozymes -- RNA therapies -- small interfering RNA -- U1 interfering RNA; 615.1
• DOI: 10.1080/17460441.2022.2117296
• Languages: English
• ISSNs: 1746-0441

Abstract

ABSTRACT: 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.