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Alnylam, AlCana Researchers Detail Lipid-development Effort

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Alnylam Pharmaceuticals researchers last month published details on the company’s efforts to improve lipid nanoparticles for RNAi drug delivery.

In Molecular Therapy, the scientists noted that the key challenge to improving the delivery vehicles “was to introduce biodegradable functionality in such a way as to promote rapid in vivo metabolism into more hydrophilic, water-soluble products, while maintaining the excellent potency of the most advanced lipids currently available.”

To do so, they and collaborators from AlCana Technologies designed a lipid structure so that the biocleavable groups were positioned within the hydrophobic lipid tails, according to the paper. Ester linkages were also selected due to their “simple structure, good chemical stability, and potential for rapid enzymatic cleavage in vivo,” they noted in the paper.

Overall, the lipid the team designed “incorporates biodegradability into design principles elucidated in prior structure-activity relationship studies, resulting in rapid elimination and excretion, substantial tolerability, and excellent potency” in rodents and non-human primates, they wrote. “To our knowledge, this is the first demonstration of a biodegradable lipid with an efficacy profile on par with that of the most advanced lipids currently available for siRNA delivery.”

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