SAN DIEGO, Nov. 17, 2014 /PRNewswire/ -- Solstice Biologics, a company focused on the targeted delivery of nucleic acid therapeutics, today announced the publication of data demonstrating an important advance in the critical hurdle of delivering ribonucleic acid interference (RNAi) therapeutics. The study, performed by Solstice co-founder, Steven F. Dowdy, Ph.D., professor in the Department of Cellular and Molecular Medicine at University of California, San Diego (UCSD), was published in the journal Nature Biotechnology and details a novel synthetic approach that disguises RNAi drugs and thereby significantly improves delivery into cells. Once inside targeted cells, the RNAi molecule is unmasked and disrupts specific biological pathways responsible for disease. The technology served as the starting point for Solstice's RNAi delivery technology.
RNAi therapeutics represents a promising area of pharmaceutical research for their ability to block the production of proteins implicated in disease. However, RNAi-based drugs have numerous charged phosphate groups that not only prevent efficient transport into cells, but are also prone to degradation by nucleases. Although recent improvements in delivery have led to multiple liver specific clinical trials, unfortunately those approaches cannot be extended to RNAi delivery in other tissues beyond the liver. Consequently, RNAi delivery remains the critical hurdle for the field.
The breakthrough research described in this article was led by Dowdy and the research was funded by the W.M. Keck Foundation, U.S. Department of Defense, Leukemia & Lymphoma Society, Pardee Foundation and Howard Hughes Medical Institute. Solstice has an exclusive licensing agreement with UCSD for all intellectual property related to this discovery.
"This work from the lab of Solstice's scientific co-founder set the foundation for important advances that Solstice has made in the last 18 months. It is exciting to see this tour de force study get the peer reviewed recognition it deserves," said Lou Tartaglia, Ph.D., Solstice president and chief executive officer.
Dowdy and his team added neutral phosphotriester groups that mask the problematic phosphate charges on RNAi drugs. However, once inside the cell, enzymes cleaved the neutral phosphotriester groups to expose a charged and active RNAi molecule that shut down production of the target disease protein. Such a drug that is converted to its active form by a normal metabolic process is referred to as a prodrug. "While my lab at UCSD spent eight years laying down the foundation for phosphotriester modified RNAi molecules, Solstice has taken the technology to a whole new level," said Dowdy.
"The general principles described in this study served as a critical starting point for Solstice to rapidly develop more advanced generations of the technology with unique pharmaceutical properties," said Curt Bradshaw, Ph.D., Solstice co-founder and chief scientific officer. Building on the Dowdy lab's work, the Solstice team altered the mechanism of prodrug release and introduced important new structural features. These next generation improvements have enhanced key performance characteristics such as deliverability, potency, stability and ease of synthesis. "Our most recent advances are now being directed to deliver nucleic acid therapeutics to non-liver tissues," added Bradshaw.
The paper entitled, "Efficient delivery of RNAi prodrugs containing reversible charge-neutralizing phosphotriester backbone modifications," is available via Advance Online Publication on Nature Biotechnology's website at: http://dx.doi.org/10.1038/nbt.3078
About Solstice Biologics
Solstice Biologics is a private company focused on solving the problem of targeting and delivery of nucleic acid therapeutics. The company is developing RNAi therapeutics that can enter different cell types and deliver on the promise of nucleic acid-based therapeutics. Solstice is backed by venBio and Aeris Capital AG. Visit www.solsticebio.com for more information.
SOURCE Solstice Biologics