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.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Suk JS,Suh J,Choy K,Lai SK,Fu J,Hanes Jdoi
10.1016/j.biomaterials.2006.05.013subject
Has Abstractpub_date
2006-10-01 00:00:00pages
5143-50issue
29eissn
0142-9612issn
1878-5905pii
S0142-9612(06)00455-8journal_volume
27pub_type
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