Gene delivery to differentiated neurotypic cells with RGD and HIV Tat peptide functionalized polymeric nanoparticles

Jung Soo Suk, Junghae Suh, Kokleong Choy, Samuel K. Lai, Jie Fu, Justin Hanes

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)5143-5150
Number of pages8
JournalBiomaterials
Volume27
Issue number29
DOIs
StatePublished - Oct 2006

Keywords

  • CNS diseases
  • Gene therapy
  • Polyethylenimine (PEI)
  • Polymers

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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