Format

Send to

Choose Destination

See 1 citation found using an alternative search:

Nat Biotechnol. 2010 Feb;28(2):172-6. doi: 10.1038/nbt.1602. Epub 2010 Jan 17.

Rational design of cationic lipids for siRNA delivery.

Author information

1
Tekmira Pharmaceuticals, Burnaby, British Columbia, Canada. ssemple@tekmirapharm.com

Abstract

We adopted a rational approach to design cationic lipids for use in formulations to deliver small interfering RNA (siRNA). Starting with the ionizable cationic lipid 1,2-dilinoleyloxy-3-dimethylaminopropane (DLinDMA), a key lipid component of stable nucleic acid lipid particles (SNALP) as a benchmark, we used the proposed in vivo mechanism of action of ionizable cationic lipids to guide the design of DLinDMA-based lipids with superior delivery capacity. The best-performing lipid recovered after screening (DLin-KC2-DMA) was formulated and characterized in SNALP and demonstrated to have in vivo activity at siRNA doses as low as 0.01 mg/kg in rodents and 0.1 mg/kg in nonhuman primates. To our knowledge, this represents a substantial improvement over previous reports of in vivo endogenous hepatic gene silencing.

PMID:
20081866
DOI:
10.1038/nbt.1602
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center