Open Collections

Synthesis of novel ionisable lipids for the targeted delivery of siRNA

University of British Columbia

RNA interference has been proven to be a powerful tool for gene probing and has also great therapeutic potential. In order for it to be clinically relevant, methods need to be developed for the targeted delivery of siRNA. Lipid nanoparticles (LNPs) have emerged as superior siRNA carrier agents with demonstrated efficacy in vivo. Such nanoparticles incorporate structurally novel lipids, the progenitor of which was conceived and first synthesized in this group. All such lipids bear an ionisable head group in the form of a tertiary amine. Protonation of this amino group is believed to promote a better association with the nucleic acid in the LNP construct. Extensive studies are currently underway in our laboratories to elucidate the structure-activity relationship of such lipids, and to produce lipids with better properties. In this work, we demonstrate the synthesis of five novel ionisable lipids, bearing different tertiary amine groups, for the purposes of siRNA encapsulation and delivery. Biological results showed one of them to be as effective as the benchmark lipid used in the field, whereas the others were not effective.

Text

2016-08-24

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/58939

Chemistry

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/