Document Detail

An amino acid-based amphoteric liposomal delivery system for systemic administration of siRNA.
MedLine Citation:
PMID:  21505423     Owner:  NLM     Status:  MEDLINE    
We demonstrate a systematic and rational approach to create a library of natural and modified, dialkylated amino acids based upon arginine for development of an efficient small interfering RNA (siRNA) delivery system. These amino acids, designated DiLA₂ compounds, in conjunction with other components, demonstrate unique properties for assembly into monodisperse, 100-nm small liposomal particles containing siRNA. We show that DiLA₂-based liposomes undergo a pH-dependent phase transition to an inverted hexagonal phase facilitating efficient siRNA release from endosomes to the cytosol. Using an arginine-based DiLA₂, cationic liposomes were prepared that provide high in vivo siRNA delivery efficiency and are well-tolerated in both cell and animal models. DiLA₂-based liposomes demonstrate a linear dose-response with an ED₅₀ of 0.1 mg/kg against liver-specific target genes in BALB/c mice.
Roger C Adami; Shaguna Seth; Pierrot Harvie; Rachel Johns; Renata Fam; Kathy Fosnaugh; Tianying Zhu; Ken Farber; Michael McCutcheon; Thomas T Goodman; Yan Liu; Yan Chen; Erin Kwang; Michael V Templin; Greg Severson; Tod Brown; Narendra Vaish; Feng Chen; Patrick Charmley; Barry Polisky; Michael E Houston
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Publication Detail:
Type:  Journal Article     Date:  2011-04-19
Journal Detail:
Title:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  19     ISSN:  1525-0024     ISO Abbreviation:  Mol. Ther.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-01     Completed Date:  2011-09-30     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1141-51     Citation Subset:  IM    
Marina Biotech, Inc., Bothell, Washington, USA.
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MeSH Terms
Amino Acids / chemistry*
Hep G2 Cells
Liposomes / chemistry*
Mice, Inbred BALB C
RNA, Small Interfering / genetics*
Reg. No./Substance:
0/Amino Acids; 0/Liposomes; 0/RNA, Small Interfering

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