title: Progress in gene delivery by cationic lipids: guanidinium-cholesterol-based systems as an example.
abstract: Artificial self-assembling systems are currently widely investigated as an alternative approach to recombinant viruses for gene transfection in vitro and in vivo. Cationic lipids are particularly attractive, as a great variety of well-characterized reagents can be synthesized from there. Over the last few years, numerous cationic lipid systems have been developed and shown to be efficient for in vitro transfection. However, although some promising results have been reported in the in vivo setting (even in clinical gene therapy trials in man), the in vivo use of cationic lipid-based systems is still problematic, especially when considering the systemic route of administration. Herein, we summarize our own research on a particular class of cationic lipids, cholesterol derivatives characterized by polar headgroups with guanidinium functions, in order to illustrate the basic principles of and the positive results already obtained by cationic lipid-mediated gene delivery as well as the remaining problems that need to be urgently resolved, particularly as regards the systemic administration. In this forward-looking review, we also discuss the present efforts to develop modular systems for improved in vivo transfection. Indeed, lipid-based vectors offer the possibility to create sophisticated modular gene delivery systems capable of self-assembly via hydrophobic interaction between their components, the role of the different functional elements being to help in overcoming the distinct extracellular and cellular barriers to in vivo gene transfection into the various somatic target tissues.
authors.affiliation: INSERM U458, Hĵpital Robert Debré, Paris, France.
authors.forename: Abderrahim
authors.initials: A
authors.lastname: Aissaoui
authors.forename: Noufissa
authors.initials: N
authors.lastname: Oudrhiri
authors.forename: Laure
authors.initials: L
authors.lastname: Petit
authors.forename: Michelle
authors.initials: M
authors.lastname: Hauchecorne
authors.forename: Erwan
authors.initials: E
authors.lastname: Kan
authors.forename: Matthieu
authors.initials: M
authors.lastname: Sainlos
authors.forename: Sébastien
authors.initials: S
authors.lastname: Julia
authors.forename: Jean
authors.initials: J
authors.lastname: Navarro
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vigneron
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Lehn
authors.forename: Pierre
authors.initials: P
authors.lastname: Lehn
mesh_terms: D000818:Animals; D002412:Cations / Q000008:administration & dosage / Q000737:chemistry; D002784:Cholesterol / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D019791:Guanidine / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D014162:Transfection / Q000379:methods
chemical_list: D002412:Cations; D002784:Cholesterol; D019791:Guanidine