The Kastrup Lab’s approach targets the problem at its source. Researchers developed an experimental therapy using small RNA molecules (called siRNA) that essentially turn down production of the gene responsible for producing PAI-1. To deliver the therapy, they packaged these siRNA molecules inside lipid nanoparticles, microscopic fat-based capsules that can carry the therapeutics directly into patient cells.

In testing, the therapy dramatically reduced PAI-1 levels, offering a promising new strategy for preventing clots without the bleeding risks that come with conventional blood thinners. It also dramatically prolonged lifespan in fast-aging mice models without thrombosis.  

“Current treatments often require long-term blood thinners that can increase the risk of bleeding,” says Kastrup. “A therapy that lowers PAI-1 with a single dose lasting 10 days could offer a more targeted and long-term alternative with fewer side effects.” Kastrup and his team imagine a future where older patients live longer, healthier lives while reducing complications from clot-related conditions such as heart attacks, strokes, and deep vein thrombosis.

The work also highlights the translational focus of research at Versiti Blood Research Institute, where scientists are combining expertise in blood biology with emerging technologies to develop new therapeutic approaches.

“This type of cutting-edge, translational research is exactly why VBRI is a leader in developing new strategies to prevent and treat blood-released diseases,” says Kastrup.

The team behind this study include: Francesca Ferraresso, PhD, Chad Skaer, Zimu Wei, Manoj Paul, PhD, Woosuk Steve Hur, PhD, Hongyin Yu, Monica Seadler, MD, Taylor Chen, Wen Dai, Catherine Lapointe, Laura Ketelboeter, PhD, Hayley Lund, Geoffrey Rodriguez, MD, Lih Jiin Juang, PhD, Amy Strilchuk, PhD, Youjie Zhang, Pieter Cullis, PhD, Mitchell Dyer, PhD, Allison Gerras, MS, DVM, DACVP, Qizhen Shi, MD, PhD, James Luyendyk, PhD, Matthew Flick, PhD, and Christian Kastrup, PhD.