Document Detail


Rapid Discovery of Potent siRNA-Lipid-Nanoparticles Enabled by Controlled Microfluidic Formulation.
MedLine Citation:
PMID:  22475086     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Discovery of potent new materials for in vivo delivery of nucleic acids depends upon successful formulation of the active molecules into a dosage form suitable for the physiological environment. Due to the inefficiencies of current formulation methods, materials are usually first evaluated for in vitro delivery efficacy as simple ionic complex with the nucleic acids (lipoplexes). The predictive value of such assays, however, has never been systematically studied. Here for the first time, by developing a microfluidic method that allowed the rapid preparation of high quality siRNA-containing lipid nanoparticles(LNPs) for a large number of materials, we showed that gene silencing assays employing lipoplex result in a high rate (~90%) of false negatives that can largely be avoided through formulation. Seven novel materials with in vivo gene silencing potency >90% at a dose of 1.0 mg/kg in mice were discovered. This method will facilitate the discovery of next generation reagents for LNP-mediated nucleic acid delivery.
Authors:
Delai Chen; Kevin T Love; Yi Chen; Ahmed A Eltoukhy; Christian J Kastrup; Gaurav Sahay; Alvin Jeon; Yizhou Dong; Kathryn A Whitehead; Daniel G Anderson
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-5
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  -     ISSN:  1520-5126     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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