Lipid mania

CAMBRIDGE, Mass.—Alnylam Pharmaceuticals Inc. recently announced the publication of a new study in Nature Biotechnology by Alnylam scientists and collaborators from the David H. Koch Institute for Integrative Cancer Research at MIT that documents the design and synthesis of a new class of lipid-based molecules called "lipidoids" that were used to form novel nanoparticle formulations for systemic delivery of RNAi therapeutics.

The studies showed successful delivery of siRNAs in multiple animal species, and showed potent, specific and durable effects on gene expression in multiple tissues, such as liver, lung and peritoneal macrophages.

The research also reportedly demonstrates applications of the same technology for delivering miRNA therapeutics—specifically the delivery of anti-miRNA oligonucleotides or "antagomirs" used to suppress miRNA activity.

"RNA interference is a tool that has a lot of people excited [because] we hope it will provide a new method to control almost any gene in the body," says Dr. Daniel Anderson of the Koch institute, the senior author of the paper published in Nature Biotechnology.

"The successful systemic delivery of RNAi therapeutics remains an important objective in our efforts to bring these innovative medicines to patients," adds Dr. Victor Kotelianski, VP of research at Alnylam. "[This] new research could pave an entirely new path for efficient delivery of RNAi therapeutics in a broad range of clinical applications.

Further, this new work builds on our existing delivery efforts both in-house, and with collaborators including MIT, Tekmira, Protiva, and others."

As part of their work, the researchers created a library of more than 1,000 lipidoids, using a combinatorial synthesis scheme that allows for simple, high-speed production. A major advantage of these chemical methods, Anderson says, is they facilitate production of a large variety of different molecules, which could be customized for different RNAi therapies and drug-delivery problems.

"For the first time, we've got a lot of formulations to choose from," Anderson notes. "In the next five years, we expect to push this technology forward in a number of different clinical and drug-delivery applications." DDN