It looks like fledgling biotech Traversa Therapeutics has found its first big pharma partner. Sanofi-Aventis signed on to use La Jolla, Calif.-based Traversa’s siRNA delivery technology, which it calls by the unwieldy abbreviation “PTD-DRBD.” We first wrote about Traversa last fall, as part of a larger piece about the challenges of delivering RNAi. The company is taking quite a vastly different approach to delivering strands of siRNA into cells of interest than its competitors, which are primarily focused on developing different flavors of lipid nanoparticles. Rather than create shells around the genetic payload using various lipid components, which are notoriously hard to direct to specific tissues, Traversa takes advantage of a natural process called macropinocytosis. What’s macropinocytosis, you ask? Basically, it is the mechanism that all cells use to swallow large amounts of fluid or other material. Think of it as the cell’s Ms. Pacman mode.
Using technology developed by UCSD professor Steven Dowdy, Traversa binds siRNA to the peptide transduction domain (PTD), a protein fragment that controls macropinocytosis.
As we wrote last fall, that PTD isn’t quite enough to get in to the cell:
“The domain, however, contains only eight positive charges, not enough to trump the 40 negative charges on siRNA, so the two can’t be directly linked without causing molecules to aggregate, Dowdy explains. Traversa’s solution is a fusion protein that links the PTD to another positively charged protein fragment that is noncovalently bound to the siRNA. By coating siRNA with the fusion protein, it’s charge is masked, enabling it to reach its target. Once inside the cell, the drop in pH causes the release of siRNA from its delivery vehicle.”
Like all siRNA delivery systems, there’s still some tweaking to be done to get this to work. Having a big pharma partner sign on to play with a system usually helps push that tweaking process along. But if it works, Dowdy believes the method can get siRNA into any cell type, which could open the door to developing drugs that address pretty much any disease you’re after.
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