title: Synthetic vectors for gene delivery: An overview of their evolution depending on routes of administration.
abstract: Nucleic acid delivery constitutes an emerging therapeutic strategy to cure various human pathologies. This therapy consists of introducing genetic material into the whole body or isolated cells to correct a cellular abnormality or disfunction. As with any drug, the main objective of nucleic acid delivery is to establish optimal balance between efficacy and tolerance. The methods of administration and the vectors used are selected depending on whether the goal of treatment is the production of an active protein; the replacement of a missing or inactive gene; or the combat of acquired diseases, such as cancer or AIDS. In that sense, synthetic vectors represent a valuable solution because they are well characterized, their structure can be fine tuned, and their potential toxicity can be reduced, since toxicity depends on the composition of the formulations. Here we review various synthetic vectors for gene delivery and address the question of their biodistribution as a function of the route of administration. We highlight the modifications to vectors structure and formulations necessary to overcome the major hurdles limiting the effectiveness of nucleic acid therapies.
authors.affiliation: Unité INSERM 1078; Université de Bretagne Occidentale; Université Européenne de Bretagne, Faculté de Médecine, Brest, France.
authors.forename: Nawal
authors.initials: N
authors.lastname: Belmadi
authors.affiliation: Centre de Biophysique Moléculaire; CNRS UPR4301; Université d'Orléans, Orléans, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Midoux
authors.affiliation: Plateforme SynNanoVect, Biogenouest, SFR 148 ScInBioS; Université de Bretagne Occidentale, Faculté de Médecine, Brest, France.|Unité INSERM 991; Université de Rennes 1, Rennes, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Loyer
authors.affiliation: Unité INSERM 1066; Université d'Angers, Angers, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Passirani
authors.affiliation: Centre de Biophysique Moléculaire; CNRS UPR4301; Université d'Orléans, Orléans, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Pichon
authors.affiliation: Unité INSERM 1078; Université de Bretagne Occidentale; Université Européenne de Bretagne, Faculté de Médecine, Brest, France.|Plateforme SynNanoVect, Biogenouest, SFR 148 ScInBioS; Université de Bretagne Occidentale, Faculté de Médecine, Brest, France.
authors.forename: Tony
authors.initials: T
authors.lastname: Le Gall
authors.affiliation: Plateforme SynNanoVect, Biogenouest, SFR 148 ScInBioS; Université de Bretagne Occidentale, Faculté de Médecine, Brest, France.|UMR CNRS 6521; Université de Bretagne Occidentale; Université Européenne de Bretagne, Faculté des Sciences, Brest, France.
authors.forename: Paul-Alain
authors.initials: PA
authors.lastname: Jaffres
authors.affiliation: Unité INSERM 1078; Université de Bretagne Occidentale; Université Européenne de Bretagne, Faculté de Médecine, Brest, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lehn
authors.affiliation: Unité INSERM 1078; Université de Bretagne Occidentale; Université Européenne de Bretagne, Faculté de Médecine, Brest, France. tristan.montier@univ-brest.fr.|Plateforme SynNanoVect, Biogenouest, SFR 148 ScInBioS; Université de Bretagne Occidentale, Faculté de Médecine, Brest, France. tristan.montier@univ-brest.fr.|Laboratoire de génétique moléculaire et d'histocompatibilité, CHRU de Brest, Brest; DUMG, Université de Bretagne Occidentale, Faculté de Médecine, Brest, France. tristan.montier@univ-brest.fr.
authors.forename: Tristan
authors.initials: T
authors.lastname: Montier
mesh_terms: D000818:Animals; D002412:Cations; D002460:Cell Line; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008055:Lipids; D051379:Mice; D058615:Synthetic Biology; D014018:Tissue Distribution
chemical_list: D002412:Cations; D008055:Lipids
keywords: Biodistribution; Cellular barriers; Gene delivery; Routes of administration; Synthetic vectors