Under an ARPA-H pilot award of up to $4.4 million over one year, the PROPEL program aims to control gene expression through RNA structure, building logic-gated RNA therapies that switch on only where and when intended, without altering the genome
CAMBRIDGE, Mass., Sept. 1, 2026 /PRNewswire-PRWeb/ -- RNAV8 Bio (pronounced "Renovate Bio"), a biotechnology company applying AI-driven design and laboratory validation to engineer more predictable mRNA medicines, today announced that it has been selected, as part of a team led by the Rouskin Lab at Harvard Medical School with the Weissman Lab at MIT / the Whitehead Institute, to receive funding from the Advanced Research Projects Agency for Health (ARPA-H) for PROPEL (Programmable RNA for Optimal Precision in Therapeutic Efficacy and Localization). The award, a one-year ARPA-H pilot of up to $4.4 million, will fund a program to turn RNA's natural folding behavior into a precise, drug-tunable control layer for a new generation of RNA medicines. PROPEL is led by ARPA-H Program Manager Shannon Greene, Ph.D.
"The promise of mRNA has always been that it's programmable, but in practice the relationship between an RNA's sequence and chemistry and what it actually does has been hard to predict," said Devan Shah, Founder and Chief Executive Officer of RNAV8 Bio. "Our work with the Rouskin and Weissman labs is aimed squarely at that gap: learning the rules that connect sequence to function, and building them into logic-gated constructs that express where and when they should. Just as important, every element we discover stays answerable in the format a medicine actually ships in. We're proud to help carry this science from a regulatory element toward a real therapeutic."
Within PROPEL, RNAV8 Bio focuses on the therapeutic format itself. It screens protein output from pools of transfected mRNA, engineers UTRs in the delivery format, and validates results at the cargo level, for example driving cell-type-selective expression of therapeutic payloads such as gene-editing enzymes or CAR constructs.
Most medicines act wherever their chemistry carries them, and most genetic therapies work by permanently changing DNA. PROPEL pursues a different kind of control. An RNA molecule's untranslated regions (UTRs) fold into structures, and those structures set how much protein the message produces. When a small molecule binds one of those folds, the structure rearranges and the output changes, turning a dose into 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.
"For decades we've read RNA sequence as a set of instructions for making a protein. What we can now read, at the scale of thousands of sequences at once, is how that sequence folds, and how a small molecule can change the fold and, with it, the output," said Silvi Rouskin, Ph.D., Assistant Professor of Microbiology, Harvard Medical School. "Human cells almost certainly already use this kind of structural control; we've simply never had the tools to find it systematically. PROPEL is our attempt to map it and put it to work."
PROPEL pursues this along two lines of work that share a single screening pipeline. Discovery searches human RNA for naturally occurring elements whose structure responds to a metabolite or an FDA-approved drug, native regulation reachable with existing, well-tolerated molecules. Engineering installs regulatory elements into therapeutic mRNA so that a single construct is selective by cell type through its sequence and tunable through its structure. Both rely on high-throughput mapping of how an RNA's folds shift when a ligand binds, which flags the elements that regulate protein output before the team tests which ones a small molecule can move.
The Weissman Lab contributes massively parallel screens of human untranslated-region elements across cell types, measuring which ones set expression where.
"The untranslated regions flanking a message are among the most powerful and least exploited levers on how much protein a cell makes," said Jonathan Weissman, Ph.D., Professor of Biology, MIT and Member, Whitehead Institute. "By screening these elements across cell types, we can begin to tell which ones set expression where, turning a vague notion of 'regulation' into a defined, reusable parts list. That is what makes a control layer generalizable rather than a one-off trick."
By the end of its initial phase, the collaboration aims to produce resources that do not exist today: a map of how thousands of human RNA sequences respond to small molecules, with structural models; a ranked catalogue of human UTR elements that set translation cell type by cell type; engineered UTRs that reach meaningful selectivity in a therapeutic format; and RNA sequences, natural or engineered, shown to switch structure inside human cells. Together these are meant to form a generalizable, disease-agnostic foundation for RNA medicine.
About RNAV8 Bio
RNAV8 Bio (pronounced "Renovate Bio") utilizes rational design alongside machine learning and artificial intelligence techniques to engineer mRNA functions with greater predictability. In vitro and in vivo data indicate that RNAV8's distinctive methodology has the potential to significantly enhance mRNA's therapeutic window compared to prevailing industry standards. Consequently, the company has garnered partnership traction with leading biotechnology and pharmaceutical firms, showcasing the promising impact of their approach. For more information, visit www.rnav8bio.com.
About PROPEL
Programmable RNA for Optimal Precision in Therapeutic Efficacy and Localization (PROPEL) is a program supported by ARPA-H that develops a programmable, drug-tunable control layer for RNA medicines. It brings together the Rouskin Lab at Harvard Medical School, the Weissman Lab at MIT / the Whitehead Institute, and RNAV8 Bio.
Media Contact
David Schutzman, RNAV8 Bio, 1 2036611435, [email protected], https://www.rnav8bio.com/
SOURCE RNAV8 Bio
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