Researchers at Marina Biotech have identified new DiLA2-based formulations composed of multiple DiLA2 molecules, that when paired with a UsiRNA targeting FVII mRNA in liver (hepatocytes) of mice, provided 50% inhibition (ED50) of FVII protein activity with a single systemically delivered dose of approximately 30 micrograms/kg.
In comparison, previous formulations provided ED50’s of approximately 300 micrograms/kg. This effective dosing was accompanied by an approximately 30-fold therapeutic window.
Marina Biotech president and CEO Michael French said that this breakthrough in the delivery capability further strengthens their RNAi drug discovery platform as well as their continuing discussions with potential pharma partners.
Marina Biotech chief scientific officer Barry Polisky said that this advancement in siRNA delivery efficiency, and the speed at which they were able to achieve it, validates their research team’s approach of integrating chemistry, molecular pharmaceutics, and biology to address the challenges of siRNA delivery, and continues to demonstrate the utility and diversity of our DiLA2 delivery platform.
"Our team has established a set of assays and a systematic approach to explore the large formulation space provided by the DiLA2 platform," Polisky said.
"We expect to further enhance the delivery capabilities of the platform, in particular, the identification of formulations for oncology specific indications."