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Polyethylene glycol–grafted polyethylenimine used to enhance adenovirus gene delivery
Author(s) -
Singarapu Kumar,
Pal Ivy,
Ramsey Joshua D.
Publication year - 2013
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.34483
Subject(s) - polyethylenimine , peg ratio , polyethylene glycol , materials science , gene delivery , copolymer , pegylation , genetic enhancement , polymer chemistry , biochemistry , chemistry , polymer , transfection , gene , finance , economics , composite material
Abstract An improved adenoviral‐based gene delivery vector was developed by complexing adenovirus (Ad) with a biocompatible, grafted copolymer PEG‐g‐PEI composed of polyethylene glycol (PEG) and polyethylenimine (PEI). Although an Ad‐based gene vector is considered relatively safe, its native tropism, tendency to elicit an immune response, and susceptibility to inactivating antibodies makes the virus less than ideal. The goal of the current study was to determine whether Ad could be complexed with a PEG‐g‐PEI copolymer that would enable the virus to transduce cells lacking the Ad receptor, while avoiding the issues commonly associated with PEI. A copolymer library was synthesized using 2 kDa PEG and either linear or branched PEI (25 kDa) with a PEG to PEI grafting ratio of 10, 20, or 30. The results of the study indicate that PEG‐g‐PEI/Ad complexes are indeed able to transduce CAR‐negative NIH 3T3 cells. The results also demonstrate that the PEG‐g‐PEI/Ad complexes are less toxic, less hemolytic, and more appropriately sized than PEI/Ad complexes. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.