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Lipid carriers for gene therapy.

A wide variety of lipid molecules used as gene carriers has been reported and compared over the last twenty years. This review highlights a few examples of mechanistic analysis applied to the study of lipid carriers. The modular nature of the lipid structure offers itself up to a controlled, systema... Full description

Journal Title: Current drug delivery October 2005, Vol.2(4), pp.423-428
Main Author: Hart, Stephen L
Format: Electronic Article Electronic Article
Language: English
Subjects:
DNA
ID: ISSN: 1567-2018
Link: http://search.proquest.com/docview/68831753/?pq-origsite=primo
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title: Lipid carriers for gene therapy.
format: Article
creator:
  • Hart, Stephen L
subjects:
  • Alkylation–Administration & Dosage
  • Animals–Chemistry
  • DNA–Chemistry
  • Drug Carriers–Chemistry
  • Esters–Chemistry
  • Genetic Therapy–Chemistry
  • Genetic Vectors–Chemistry
  • Humans–Chemistry
  • Lipids–Chemistry
  • Liposomes–Chemistry
  • Transfection–Chemistry
  • Drug Carriers
  • Esters
  • Lipids
  • Liposomes
  • DNA
ispartof: Current drug delivery, October 2005, Vol.2(4), pp.423-428
description: A wide variety of lipid molecules used as gene carriers has been reported and compared over the last twenty years. This review highlights a few examples of mechanistic analysis applied to the study of lipid carriers. The modular nature of the lipid structure offers itself up to a controlled, systematic analysis. Key to exploring structural variants is the understanding of the role each component and module plays in the formation of the lipoplex structure itself and their roles in the transfection pathway. Firstly, the lipid carrier must be able to package, and release into the cell its nucleic acid cargo. Uptake of lipoplexes into cells involves endocytic processes that lead inevitably to endosomal/liposomal degradation of the nucleic acid contents, unless lipid structures and designs are optimised to facilitate their release into the cytoplasm. Testing of possible endosomal escape mechanisms has led to improved lipid designs. For example, it was predicted that mixing of cationic lipids with shorter alkyl tails ( < C18) from liposomes with the endosomal bilayer during the transfection process within the endosome should promote membrane fluidity, enhancing plasmid release and transfection efficiency. This hypothesis has been borne out numerous times. "Smart" molecules that respond to cellular cues such as endosomal pH have now been developed that appear to offer exciting opportunities for the future role of lipoplexes in clinical applications of gene therapy. The variability of cultured cell and model biological systems remains a challenge in designing improved lipids of general utility.
language: eng
source:
identifier: ISSN: 1567-2018
fulltext: fulltext
issn:
  • 15672018
  • 1567-2018
url: Link


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identifierISSN: 1567-2018
subjectAlkylation–Administration & Dosage ; Animals–Chemistry ; DNA–Chemistry ; Drug Carriers–Chemistry ; Esters–Chemistry ; Genetic Therapy–Chemistry ; Genetic Vectors–Chemistry ; Humans–Chemistry ; Lipids–Chemistry ; Liposomes–Chemistry ; Transfection–Chemistry ; Drug Carriers ; Esters ; Lipids ; Liposomes ; DNA
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descriptionA wide variety of lipid molecules used as gene carriers has been reported and compared over the last twenty years. This review highlights a few examples of mechanistic analysis applied to the study of lipid carriers. The modular nature of the lipid structure offers itself up to a controlled, systematic analysis. Key to exploring structural variants is the understanding of the role each component and module plays in the formation of the lipoplex structure itself and their roles in the transfection pathway. Firstly, the lipid carrier must be able to package, and release into the cell its nucleic acid cargo. Uptake of lipoplexes into cells involves endocytic processes that lead inevitably to endosomal/liposomal degradation of the nucleic acid contents, unless lipid structures and designs are optimised to facilitate their release into the cytoplasm. Testing of possible endosomal escape mechanisms has led to improved lipid designs. For example, it was predicted that mixing of cationic lipids with shorter alkyl tails ( < C18) from liposomes with the endosomal bilayer during the transfection process within the endosome should promote membrane fluidity, enhancing plasmid release and transfection efficiency. This hypothesis has been borne out numerous times. "Smart" molecules that respond to cellular cues such as endosomal pH have now been developed that appear to offer exciting opportunities for the future role of lipoplexes in clinical applications of gene therapy. The variability of cultured cell and model biological systems remains a challenge in designing improved lipids of general utility.
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