Targeted gene delivery into peripheral sensorial neurons mediated by self-assembled vectors composed of poly(ethylene imine) and tetanus toxin fragment c

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Hugo Oliveira (Author) Other; Ramon Fernandez (Author) Other; Liliana R Pires (Author) Other; Cristina C L Martins (Author) Other; Sergio Simoes (Author) Other; Mario A Barbosa (Author) FEUP; Ana P Pego (Author) FEUP

Journal

Title: Journal of Controlled Release

Vol. 143

Pages: 350-358

ISSN: 0168-3659

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 32 Citations

Scopus - 38 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-003-6RH

DOI: 10.1016/j.jconrel.2010.01.018

Abstract (EN): A simple, safe and efficient system that can specifically transfect peripheral sensorial neurons can bring new answers to address peripheral neuropathies. A multi-component non-viral gene delivery vector targeted to peripheral nervous system cells was developed, using poly(ethylene imine) (PEI) as starting material. A binary DNA/polymer complex based on thiolated PEI (PEISH) was optimized, considering complex size and zeta potential and the ability to transfect a sensorial neuron cell line (ND7/23). The 50 kDa non-toxic fragment from tetanus toxin (HC), which has been previously shown to interact specifically with peripheral neurons and to undergo retrograde transport, was grafted to the complex core via a bifunctional PEG (HC-PEG) reactive for the thiol moieties present in the complex surface. Several formulations of HC-PEG ternary complexes were tested for targeting, by assessing the extent of cellular internalization and levels of transfection, in both the ND7/23 and NIH 3 T3 (fibroblast) cell lines. Targeted gene transfer to the neuronal cell line was observed for the complex formulations containing 5 and 7.5 mu g of HC-PEG. Finally, our results demonstrate that the developed ternary vectors are able to transfect primary cultures of dorsal root ganglion dissociated neurons in a targeted manner and elicit the expression of a relevant neurotrophic factor.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9