| Literature DB >> 23614580 |
Thazha P Prakash1, Walt F Lima, Heather M Murray, Sayda Elbashir, William Cantley, Don Foster, Muthusamy Jayaraman, Alfred E Chappell, Muthiah Manoharan, Eric E Swayze, Stanley T Crooke.
Abstract
We evaluated the abilities of an antisense oligonucleotide (ASO), a small interfering RNA (siRNA), and a single-stranded siRNA (ss-siRNA) to inhibit expression from the PTEN gene in mice when formulated identically with lipid nanoparticles (LNPs). Significantly greater reductions in levels of PTEN mRNA were observed for LNP-formulated agents compared to unformulated drugs when gene silencing was evaluated after a single dose in the livers of mice. An unformulated ss-siRNA modified with a metabolically stable phosphate mimic 5'-(E)-vinylphosphonate showed dose-dependent reduction of PTEN mRNA in mice, albeit at doses significantly higher than those observed for formulated ss-siRNA. These results demonstrate that LNPs can be used to deliver functional antisense and ss-siRNA therapeutics to the liver, indicating that progress in the field of siRNA delivery is transferable to other classes of nucleic acid-based drugs.Entities:
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Year: 2013 PMID： 23614580 DOI： 10.1021/cb4001316
Source DB: PubMed Journal: ACS Chem Biol ISSN： 1554-8929 Impact factor: 5.100