Document Detail


Self-Assembly of Stable Monomolecular Nucleic Acid Lipid Particles with a Size of 30 nm.
MedLine Citation:
PMID:  22694262     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The design of efficient nucleic acid complexes is key to progress in genetic research and therapies based on RNA interference. For optimal transport within tissue and across extracellular barriers, nucleic acid carriers need to be small and stable. In this paper we prepare and characterize mono-Nucleic Acid Lipid Particles (mono-NALPs). The particles consist of single short double stranded oligonucleotides or single siRNA molecules each encapsulated within a closed shell of a cationic-zwitterionic lipid bilayer, furnished with an outer polyethylene glycol (PEG) shield. The particles self-assemble by solvent exchange from a solution containing nucleic acid mixed with the four lipid components DOTAP, DOPE, DOPC and DSPE-PEG(2000). Using fluorescence correlation spectroscopy we monitor the formation of mono-NALPs from short double stranded oligonucleotides or siRNA and lipids into monodisperse particles of approximately 30 nm in diameter. Small angle neutron and X-ray scattering and transmission electron microscopy experiments substantiate a micelle-like core-shell structure of the particles. The PEGylated lipid shell protects the nucleic acid core against degradation by nucleases, sterically stabilizes the mono-NALPs against disassembly in collagen networks and prevents non-specific binding to cells. Hence PEG-lipid shielded mono-NALPs are the smallest stable siRNA lipid system possible and may provide a structural design to be build upon for the development of novel nucleic acid delivery systems with enhanced biodistribution in vivo.
Authors:
Sophia Rudorf; Joachim O Radler
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-13
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  -     ISSN:  1520-5126     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-14     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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