title: Gene delivery to differentiated neurotypic cells with RGD and HIV Tat peptide functionalized polymeric nanoparticles.
abstract: A number of neurodegenerative disorders may potentially be treated by the delivery of therapeutic genes to neurons. Nonviral gene delivery systems, however, typically provide low transfection efficiency in post-mitotic differentiated neurons. To uncover mechanistic reasons for this observation, we compared gene transfer to undifferentiated and differentiated SH-SY5Y cells using polyethylenimine (PEI)/DNA nanocomplexes. Differentiated cells exhibited substantially lower uptake of gene vectors. To overcome this bottleneck, RGD or HIV-1 Tat peptides were attached to PEI/DNA nanocomplexes via poly(ethylene glycol) (PEG) spacer molecules. Both RGD and Tat improved the cellular uptake of gene vectors and enhanced gene transfection efficiency of primary neurons up to 14-fold. RGD functionalization resulted in a statistically significant increase in vector escape from endosomes, suggesting it may improve gene delivery by more than one mechanism.
authors.affiliation: Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Jung Soo
authors.initials: JS
authors.lastname: Suk
authors.forename: Junghae
authors.initials: J
authors.lastname: Suh
authors.forename: Kokleong
authors.initials: K
authors.lastname: Choy
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Lai
authors.forename: Jie
authors.initials: J
authors.lastname: Fu
authors.forename: Justin
authors.initials: J
authors.lastname: Hanes
mesh_terms: D001672:Biocompatible Materials; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D015696:Gene Products, tat; D018014:Gene Transfer Techniques; D006678:HIV / Q000235:genetics; D006801:Humans; D009474:Neurons / Q000166:cytology; D009842:Oligopeptides; D010446:Peptide Fragments / Q000235:genetics; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D001672:Biocompatible Materials; D015696:Gene Products, tat; D009842:Oligopeptides; D010446:Peptide Fragments; D054322:tat Gene Products, Human Immunodeficiency Virus; C047981:arginyl-glycyl-aspartic acid