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November 5, 2009 7:13 AM ET

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Alnylam Pharma presents new pre-clinical data on RNAi therapeutics at Oligonucleotides Therapeutics Society meeting Co announces that it presented new data related to its overall delivery research efforts including the rational design of Mimetic Lipoprotein Particles, or MLPs, a novel technology for the systemic delivery of small interfering RNAs, or siRNAs, the molecules that mediate RNAi. In addition, Alnylam scientists and collaborators presented additional new data on systemic delivery and provided an update on RNA activation technology. These new data were presented at the 5th Oligonucleotide Therapeutics Society/19th Antisense Joint Symposium held November 3-6, 2009 in Fukuoka, Japan. In a poster titled "Lipophilic siRNA Delivery by Reconstituted Lipoprotein Particles In Vivo" Tomoko Nakayama, Ph.D., Associate Director, Research at Alnylam, presented for the first time the rational design and characterization of MLPs as an RNAi delivery platform. MLPs were designed to mimic the physiologic properties of endogenous lipoprotein particles and were engineered using recombinant human apolipoprotein A1 or recombinant human apolipoprotein E, phosphatidylcholine, and a cholesterol-conjugated siRNA. The resulting MLPs had biophysical properties comparable to normal high-density lipoprotein particles including a mean diameter size of approximately 10 nm. The stoichiometry for siRNA:particle loading ratio was observed to be 1:1. The reported in vivo studies were performed in mice using MLPs with chol-siRNAs targeting apolipoprotein B, the major apolipoprotein involved in the metabolism of low-density lipoprotein cholesterol. Administration of the MLP resulted in silencing of the apoB mRNA by up to 80% with an associated 50 to 80% reduction in levels of plasma apoB protein and cholesterol in mice. These data also demonstrated significant improvements in the potency of apoB silencing when using MLP-delivery of siRNAs as compared with use of chol-siRNAs alone. The study further demonstrated that apoE-MLP was more effective in delivering siRNAs than apoA-MLPs, at least as measured for the silencing of the liver-expressed target gene.

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