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Alnylam and MIT Collaborators Discover Novel “Core-Shell” Nanoparticles for Systemic Delivery of RNAi Therapeutics

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Alnylam Pharmaceuticals, Inc., together with collaborators at the Massachusetts Institute of Technology (MIT), have announced the publication of new paper describing discovery of “core-shell” nanoparticles for systemic delivery of RNAi therapeutics.

The core-shell nanoparticles were generated using a high-throughput polymer synthesis strategy and screened for intracellular delivery applications including siRNA delivery.

These findings, published in the Proceedings of the National Academy of Sciences (Siegwart et al., PNAS, 2011, doi: 10.1073/pnas.1106379108) allow for the development of novel nanoparticles that have optimal chemical and physical properties for effective intracellular delivery of RNAi therapeutics.

“Continued progress in delivery of RNAi therapeutics requires broad-based efforts around novel lipids, conjugates, and polymers. In the current study, core-shell nanoparticles were discovered using combinatorial approaches to identify novel materials for siRNA delivery,” said Kevin Fitzgerald, Ph.D., Senior Director of Research at Alnylam. “These findings further expand our systemic delivery platform to achieve the broadest applications of RNAi therapeutics.”

“Together with our collaborators at Alnylam, we continue to make exciting progress on delivery of RNAi therapeutics,” said Dan Anderson, Ph.D., of the David H. Koch Institute for Integrative Research at MIT. “Importantly, these new data on core-shell nanoparticles highlight non-lipid approaches for siRNA delivery with opportunities for further optimization.”

Specifically, this study evaluated a library of over 1,500 chemically diverse nanoparticles as drug delivery vehicles, with precise control over particle size, chemical composition and architecture.

The physical and chemical properties of materials can have controlling effects on their utility as nanotherapeutics and the findings revealed that certain chemical functionalities may be advantageous for polymer-based delivery.

Initial in vivo studies on one of these novel nanoparticles showed silencing of hepatocyte-specific Factor VII in a pre-clinical model. The ability to control and modify the chemical nature of the core and shell of the nanoparticle may afford utility of these materials in a wide range of drug delivery applications.