| An Amino Acid-based Amphoteric Liposomal Delivery System for Systemic Administration of siRNA. | |
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MedLine Citation:
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PMID: 21505423 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 DiLA(2) compounds, in conjunction with other components, demonstrate unique properties for assembly into monodisperse, 100-nm small liposomal particles containing siRNA. We show that DiLA(2)-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 DiLA(2), cationic liposomes were prepared that provide high in vivo siRNA delivery efficiency and are well-tolerated in both cell and animal models. DiLA(2)-based liposomes demonstrate a linear dose-response with an ED(50) of 0.1 mg/kg against liver-specific target genes in BALB/c mice. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2011-4-19 |
Journal Detail:
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Title: Molecular therapy : the journal of the American Society of Gene Therapy Volume: - ISSN: 1525-0024 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100890581 Medline TA: Mol Ther Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Marina Biotech, Inc., Bothell, Washington, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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