Document Detail


Chemical vectors for gene delivery: a current review on polymers, peptides and lipids containing histidine or imidazole as nucleic acids carriers.
MedLine Citation:
PMID:  19459843     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
DNA/cationic lipid (lipoplexes), DNA/cationic polymer (polyplexes) and DNA/cationic polymer/cationic lipid (lipopolyplexes) electrostatic complexes are proposed as non-viral nucleic acids delivery systems. These DNA-nanoparticles are taken up by the cells through endocytosis processes, but the low capacity of DNA to escape from endosomes is regarded as the major limitations of their transfection efficiency. Here, we present a current report on a particular class of carriers including the polymers, peptides and lipids, which is based on the exploitation of the imidazole ring as an endosome destabilization device to favour the nucleic acids delivery in the cytosol. The imidazole ring of histidine is a weak base that has the ability to acquire a cationic charge when the pH of the environment drops bellow 6. As it has been demonstrated for poly(histidine), this phenomena can induce membrane fusion and/or membrane permeation in an acidic medium. Moreover, the accumulation of histidine residues inside acidic vesicles can induce a proton sponge effect, which increases their osmolarity and their swelling. The proof of concept has been shown with polylysine partially substituted with histidine residues that has caused a dramatic increase by 3-4.5 orders of magnitude of the transfection efficiency of DNA/polylysine polyplexes. Then, several histidine-rich polymers and peptides as well as lipids with imidazole, imidazolinium or imidazolium polar head have been reported to be efficient carriers to deliver nucleic acids including genes, mRNA or SiRNA in vitro and in vivo. More remarkable, histidylated carriers are often weakly cytotoxic, making them promising chemical vectors for nucleic acids delivery.
Authors:
Patrick Midoux; Chantal Pichon; Jean-Jacques Yaouanc; Paul-Alain Jaffrès
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  British journal of pharmacology     Volume:  157     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-22     Completed Date:  2009-08-14     Revised Date:  2010-09-27    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  166-78     Citation Subset:  IM    
Affiliation:
Centre de Biophysique Moléculaire CNRS UPR 4301 affiliated to the University of Orléans and Inserm, rue Charles Sadron, F-45071 Orléans Cedex 2, France. Patrick.midoux@cnrs-orleans.fr
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MeSH Terms
Descriptor/Qualifier:
Drug Carriers
Genetic Vectors*
Histidine / analysis*
Imidazoles / analysis*
Lipids / chemistry*
Nucleic Acids / administration & dosage*
Peptides / chemistry*
Polymers / chemistry*
Transfection*
Chemical
Reg. No./Substance:
0/Drug Carriers; 0/Imidazoles; 0/Lipids; 0/Nucleic Acids; 0/Peptides; 0/Polymers; 71-00-1/Histidine
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