title: omega-Hydrazino linear polyethylenimine: a monoconjugation building block for nucleic acid delivery.
abstract: Nonviral gene therapy requires efficient vectors that are able to deliver nucleic acids inside the targeted cell nucleus. Developing new tools for the synthesis of supramolecular vectors with improved transfection efficiency and better biodistribution is therefore a crucial issue. Here we describe the synthesis of a 140-mer linear polyethylenimine (L-PEI) terminated at one end by a highly nucleophilic hydrazine residue. This cationic polymer, whose backbone is well known for its remarkable gene-delivery efficiency, constitutes a building block for omega-regioselective conjugation to molecules through the formation of stable linkages such as the hydrazone bonds. To demonstrate the potential of the omega-hydrazino linear polyethylenimine, human serum transferrin, a ligand that is well know to improve gene-delivery systems, was used as a model of sensitive material. The blood protein was oxidized to generate an aldehyde function and was subsequently conjugated to hydrazino PEI. The new polyethylenimine-transferrin (PEI-Tf) vector was purified and was shown to condense plasmid DNA into compact superstructures compatible with cellular uptake. Finally, the cellular-binding and gene-delivery properties of PEI/DNA polyplexes incorporating different quantities of transferrin were evaluated by FACS analysis and luciferase assay.
authors.affiliation: Laboratoire de Chimie Génétique associé CNRS/ULP Strasbourg, Faculté de Pharmacie, 74 Route du Rhin, 67400 Illkirch, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Pons
authors.forename: Lila
authors.initials: L
authors.lastname: Mouhoubi
authors.forename: Abdennaji
authors.initials: A
authors.lastname: Adib
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Godzina
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Behr
authors.forename: Guy
authors.initials: G
authors.lastname: Zuber
mesh_terms: D004247:DNA / Q000737:chemistry / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D006834:Hydrazines / Q000737:chemistry* / Q000378:metabolism; D020014:K562 Cells; D046911:Macromolecular Substances; D015394:Molecular Structure; D009696:Nucleic Acids / Q000737:chemistry / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D011094:Polyethyleneimine / Q000737:chemistry* / Q000378:metabolism; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D006834:Hydrazines; D046911:Macromolecular Substances; D009696:Nucleic Acids; D014168:Transferrin; D011094:Polyethyleneimine; D004247:DNA