Harvard Medical School researchers at Massachusetts General Hospital have been selected to receive up to $25.8 million in federal funding from the Advanced Research Projects Agency for Health (ARPA-H) under its THRIVE program. The award, in the form of a contract to Mass General, will provide up to five years of support for the researchers to lead the “Vascular mEdicineS using Scalable Editing pLatform” (VESSEL) program — a multi-institutional effort to develop precision gene-editing therapies to treat rare genetic vascular diseases.
ANGEA Biotherapeutics will provide an additional $11.2 million in cost-share funding over this period, building on its prior investment to advance this work toward clinical translation. THRIVE is led by ARPA-H Program Manager Daria Fedyukina.
The VESSEL team aims to address a central and long-standing challenge in medicine: how to deliver durable, effective therapies to the vasculature. The VESSEL initiative will focus specifically on rare genetic vasculopathies — serious and underserved conditions that cause strokes, aneurysms, and heart attacks in children — for which no FDA-approved disease-modifying therapies currently exist to address the underlying genetic causes.
“We have the privilege to bring together academic and industry experts to develop the technology and breakthroughs needed to revolutionize vascular medicines and, most importantly, improve the lives of all our patients, one patient at a time,” said lead principal investigator Patricia Musolino, HMS associate professor of neurology at Mass General. “This ARPA-H award will help accelerate the necessary shift from one-off therapies, or single drug products per genetic mutation, toward platform approaches for rare genetic diseases. Our program is unique in bringing genome-editing approaches into the vascular domain.”
The VESSEL program will tackle this challenge with a fundamentally different solution: a scalable, vessel-targeted gene-editing platform that repairs disease-causing variants directly in the vascular cells that drive pathology (smooth muscle cells and endothelial cells), enabling durable, potentially one-time treatments adaptable across multiple diseases, thereby reducing the time and cost of getting each new treatment to patients. This work is informed and guided by patients, families, and advocacy groups.
The team’s goal is to create a gene-editing platform to treat some of the most severe genetic vasculopathies, such as multisystemic smooth muscle dysfunction syndrome (MSMDS), generalized arterial calcification of infancy (GACI), and Sturge-Weber syndrome, while ultimately adapting the platform to develop gene-editing treatments for additional rare and common vascular diseases. By focusing on the scalability and reusability of the technology, which combines next-generation base editors with vascular-targeted delivery platforms, the team hopes to reduce development timelines and costs and to expand patient access to these therapies.
In addition to developing potential treatments, the program aims to establish umbrella clinical trial platforms and regulatory and patient engagement frameworks — including a Genetic Vascular Diseases Network — that could help accelerate future gene-editing therapies for rare vascular diseases.
The VESSEL team is led by HMS faculty at Mass General and brings together investigators from Johns Hopkins University; Kennedy Krieger Institute; UMass Chan Medical School; the University of California, San Francisco (UCSF); the University of Alabama at Birmingham; and the Jackson Laboratories in a collaboration that integrates novel gene-editing technologies, innovative clinical trial design, and new regulatory frameworks.
“While it’s critical for the gene therapy field to find ways to lessen the time and costs of moving from diagnosis to development to administering gene therapy, it’s no easy feat,” said Musolino. “It takes collaboration across many areas of expertise to do this type of work and take on these types of scientific, manufacturing, and medical challenges.”
Also part of the THRIVE program, a project led by collaborators at the Broad Institute of MIT and Harvard has been selected to receive funding to advance gene editing for rare pediatric epilepsy.
Adapted from a Mass General Brigham news release.
