RNA therapeutics are making a tremendous impact on medicine, recently exemplified by the rapid development and deployment of mRNA vaccines to combat the COVID-19 pandemic. In addition to vaccines, RNA-targeting drugs are being developed for diseases with significant unmet medical needs.
Recent advances in genome sequencing have revealed the genetic causes of many human diseases. This information is ushering in the modern era of DNA and RNA therapeutics. While DNA targeting can result in durable and potentially permanent cures, RNA therapeutics enable tunability and reversibility without permanent off-target changes.
Several challenges must be overcome in order to realize the therapeutic potential of RNA editing to patients. Beyond exquisite guide RNA engineering that enables highly efficient and specific RNA editing, we need to address issues of delivery and manufacturing that broadly impact the field of gene therapy. In addition, we need non-clinical and clinical assays to quantify editing efficiency and transcriptome integrity to establish safety metrics to support clinical development.
In collaboration with Prashant Mali’s lab at UCSD, we published an article in Molecular Therapy to review the progress in the field of therapeutic RNA editing, highlight recent research advances, and discuss the key challenges on the path of clinical development.
Booth BJ, Nourreddine S, Katrekar D, Savva Y, Bose D, Long TJ, Huss DJ, Mali P. RNA editing: Expanding the potential of RNA therapeutics. Mol Ther. 2023 Jan 7:S1525-0016(23)00005-9. doi: 10.1016/j.ymthe.2023.01.005. Epub ahead of print. PMID: 36620962; PMCID: PMC9824937.