Trends in RNA Therapeutic Research

Thus far, many therapeutic approaches to gene modification, such as chimeric antigen receptor T-cell (CAR-T) therapy and adeno-associated virus (AAV) vector-based gene therapy, have relied upon the use of viral vectors. This may change in the future though, as RNA-based approaches under development may provide nonviral methods for modifying the genome through gene editing.

At the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting, held May 13 to 17, 2025, CGTLive® spoke with Robert Alexander Wesselhoeft, PhD, the director of RNA Therapeutics at the Gene and Cell Therapy Institute (GCTI) at Mass General Brigham (MGB), about general trends in the field of RNA therapy. Wesselhoeft emphasized his optimism for the future of the field and the potential of RNA to provide safer alternatives to viral vector based approaches.

Robert Alexander Wesselhoeft, PhD: With RNA in general, what I'm seeing is a huge number of companies that are working on in vivo CAR-T: basically making CAR T-cell therapy an injectable drug. Of course, that will be revolutionary for the CAR-T space and pretty much every CAR-T drug that's been developed or in development, of which there are many, will likely switch over to using RNA as soon as that clinical proof of concept is there. My guess is that that's going to happen within the next 2 years or so.

I think beyond in vivo CAR-T, people are still sort of thinking about different ways to apply RNA technology in general. Gene editing is one of those areas for which in many cases RNA is the preferred delivery vector of choice and so I think we'll see RNA being employed a lot in the various gene editing strategies that people are developing.

I'm very optimistic about the development of coding RNA therapeutics and nonviral delivery technology in general. I think especially even in the last few months, we've seen a lot of people moving away from classical gene therapy vectors like AAV for a variety of different reasons. It seems like nonviral gene transfer and gene expression, especially through RNA, is becoming a preferred modality where it's applicable because of its enhanced safety.