Press Release: 11/11/2026

Programmable RNA: Where the field is headed and why Massachusetts is positioned to lead

 

NOV 09, 2026

 

Contributed Post By Devan Shah, Founder and Chief Executive Officer, RNAV8 Bio

Over the past few years, mRNA medicines have moved from a promising idea to an established modality. The next question is how to give mRNA more precise control: where it acts, when it acts and how much it does. Answering it will shape the next generation of therapies, and much of the work is happening here in Massachusetts.

Delivery ex-liver brings the problem back to RNA control

Delivery is the field’s #1 challenge as to-date most mRNA therapeutics have gone into clinic for genetic liver diseases, cancer, and infectious disease. Lipid nanoparticles (“LNPs”) have thus far mostly only worked well for the liver and antigen presenting cells. Targeted LNPs (“tLNPs”) are a next-generation approach (pioneered by Boston companies like Orbital (acquired by BMS), Editas, and Tessera) which allow delivery of mRNA to T cells and hematopoietic stem cells.  

But getting RNA to the right tissue is only part of the problem. Once a message arrives, we have, to-date, limited ability to tune what it does. Dose is largely fixed at the time of administration, and expression follows a trajectory set mostly by the sequence and chemistry of the mRNA. A medicine that could be dialed up, down or off after delivery, using translation regulatory machinery or even a small molecule, would be a different kind of therapeutic. It would also widen the range of tissues and conditions RNA can safely address.

What PROPEL is trying to do

That idea is behind PROPEL, a one-year pilot funded by the Advanced Research Projects Agency for Health (ARPA-H), with up to $4.4 million. The project launched in late July 2026 and is managed by ARPA-H Program Manager Dr. Shannon Greene. It is led by Dr. Silvi Rouskin of Harvard Medical School, with collaborators from Dr. Jonathan Weissman’s lab at MIT and the Whitehead Institute. My company, RNAV8 Bio, is also part of the team. 

The premise is that RNA’s natural tendency to fold into structures can become a control switch. The untranslated regions that flank an RNA message fold into shapes that help set how much protein a cell makes. When a small molecule binds one of those folds, the structure can rearrange and the output changes. A dose becomes a dial on protein expression, without altering the genome. Bacteria use this logic openly, in elements called riboswitches. In human cells, it remains largely uncharted.

The work spans several disciplines. Dr. Rouskin’s lab can map how large numbers of RNA sequences fold, and how those folds shift when a small molecule binds. Dr. Weissman’s lab brings genome-scale screening expertise to the untranslated regions, testing which elements set expression in which cell types. RNAV8 Bio’s role is the therapeutic format itself: testing whether regulatory elements found in the lab still work in the kind of mRNA a medicine would actually use. No single group could do all of this alone.

ARPA-H’s model is built for ambitious, time-limited bets that may or may not pan out. By the end of the initial phase, the team aims to produce resources that do not exist today, including a map of how hundreds to thousands of human RNA sequences respond to small molecules and a ranked catalogue of UTR elements that set translation cell type by cell type. If the approach holds, it could become a disease-agnostic foundation for RNA medicine. Even the attempt will generate shared knowledge the field needs.

Why this is a Massachusetts story

The structure of this collaboration is as notable as its science. A Cambridge startup is working alongside Harvard Medical School, MIT and the Whitehead Institute on a federally funded program. That mix of academic depth, early-stage company agility and public funding for high-risk research is what this ecosystem does well.

It also fits a larger pattern with the recent ARPA-H THRIVE (e.g. Broad Institute-led coalition focused on genetic epilepsies) and GIVE (Mass Gen-led coalition focused on mRNA manufacturing) awards. These strengths are not automatic. They depend on continued investment in basic research, stable federal programs and a regional community that keeps the door open between institutions and startups.

What to watch

Over the next few years, expect the field to push on several fronts at once: delivery beyond the liver to an expanding list of tissues, finer control of expression and half-life, and better tools for predicting how an RNA sequence will behave before it is made. Progress on any one makes the others more valuable.

PROPEL is one early example of how these threads can come together. Whether or not its specific approach succeeds, the direction is clear: RNA medicines are becoming more programmable. Massachusetts, with its institutions, companies and public partners, is well placed to help define what comes next.