Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi
therapeutics company, today announced the publication of new data in the
journal Nature Biotechnology by Alnylam scientists and
collaborators from Tekmira Pharmaceuticals Corporation, AlCana
Technologies, Inc., and The University of British Columbia (UBC). The
new study employed a rational design approach for the discovery of novel
lipids that can be incorporated into lipid nanoparticles (LNPs) for
systemic delivery of RNAi therapeutics. This new research complements
the combinatorial chemistry-based approach recently described by Alnylam
scientists in the Proceedings of the National Academy of Sciences
(PNAS) (Love et al. (January 11, 2010) Proc. Natl Acad.
Sci. USA, 10.1073/pnas.0910603106), and highlights the power of
using multiple parallel approaches for optimizing LNPs.
“We are very excited by our continued progress in discovering new LNP
compositions that provide dramatic improvements in the systemic delivery
of RNAi therapeutics”
“We are very excited by our continued progress in discovering new LNP
compositions that provide dramatic improvements in the systemic delivery
of RNAi therapeutics,” said Victor Kotelianski, M.D., Ph.D., D.Sc.,
Senior Vice President, Distinguished Alnylam Fellow. “As compared with
our recent paper from our MIT collaboration just last month, this new
paper highlights the results of an entirely different approach using
rational design for lipid discovery. When formulated with siRNAs, these
new lipids form highly potent LNPs that augment Alnylam’s platform of
second generation LNPs. We believe that these discoveries will define
major new opportunities for Alnylam for the advancement of our pipeline.”
The new paper (Semple et al., Nature Biotechnology advance online
publication, 17 January 2010 (doi:10.1038/nbt.1602)) describes the
discovery of a novel lipid, known as “KC2,” based on a medicinal
chemistry effort to explore the structure-activity relationships in the
lipid “DLinDMA,” which is used in certain first generation LNPs such as
Tekmira’s stable nucleic acid-lipid particles (SNALP) formulations. A
large number of novel lipids were synthesized to probe the relationship
of lipid structure, such as the alkyl chain, linker, and head group
moieties, with function as determined by screening for in vivo
gene silencing activity. Additional measurements were performed to
characterize the ability of the novel lipids to mediate certain
physicochemical changes in lipid bilayers consistent with needed
disruption of endosomal membranes. In order to explore its suitability
for systemic delivery, the novel KC2 lipid was formulated with siRNA in
an LNP formulation. Specifically, the in vivo data showed that: