Discovery of siRNA lipid nanoparticles to transfect suspension leukemia cells and provide in vivo delivery capability.
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| Abstract |
As a powerful research tool, siRNA's therapeutic and target validation utility with leukemia cells and long-term gene knockdown is severely restricted by the lack of omnipotent, safe, stable, and convenient delivery. Here, we detail our discovery of siRNA-containing lipid nanoparticles (LNPs) able to effectively transfect several leukemia and difficult-to-transfect adherent cell lines also providing in vivo delivery to mouse spleen and bone marrow tissues through tail-vein administration. We disclose a series of novel structurally related lipids accounting for the superior transfection ability, and reveal a correlation between expression of Caveolins and successful transfection. These LNPs, bearing low toxicity and long stability of >6 months, are ideal for continuous long-term dosing. Our discovery represents the first effective siRNA-containing LNPs for leukemia cells, which not only enables high-throughput siRNA screening with leukemia cells and difficult-to-transfect adherent cells but also paves the way for the development of therapeutic siRNA for leukemia treatment.
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| Authors | Wei He, Michael J Bennett, Leopoldo Luistro, Daisy Carvajal, Thomas Nevins, Melissa Smith, Gaurav Tyagi, James Cai, Xin Wei, Tai-An Lin, David C Heimbrook, Kathryn Packman, John F Boylan |
| Journal | Molecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 22 Issue 2 Pg. 359-370 (Feb 2014) ISSN: 1525-0024 [Electronic] United States |
| PMID | 24002693 (Publication Type: Journal Article) |
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