Sticky "delivering-from" strategies using viral vectors for efficient human neural stem cell infection by bioinspired catecholamines.

Abstract

Controlled release of biosuprastructures, such as viruses, from surfaces has been a challenging task in providing efficient ex vivo gene delivery. Conventional controlled viral release approaches have demonstrated low viral immobilization and burst release, inhibiting delivery efficiency. Here, a highly powerful substrate-mediated viral delivery system was designed by combining two key components that have demonstrated great potential in the fields of gene therapy and surface chemistry, respectively: adeno-associated viral (AAV) vectors and adhesive catecholamine surfaces. The introduction of a nanoscale thin coating of catecholamines, poly(norepinephrine) (pNE) or poly(dopamine) (pDA) to provide AAV adhesion followed by human neural stem cell (hNSC) culture on sticky solid surfaces exhibited unprecedented results: approximately 90% loading vs 25% (AAV_bare surface), no burst release, sustained release at constant rates, approximately 70% infection vs 20% (AAV_bare surface), and rapid internalization. Importantly, the sticky catecholamine-mediated AAV delivery system successfully induced a physiological response from hNSCs, cellular proliferation by a single-shot of AAV encoding fibroblast growth factor-2 (FGF-2), which is typically achieved by multiple treatments with expensive FGF-2 proteins. By combining the adhesive material-independent surface functionalization characters of pNE and pDA, this new sticky "delivering-from" gene delivery platform will make a significant contribution to numerous fields, including tissue engineering, gene therapy, and stem cell therapy.

• Authors: Eunmi Kim, Slgirim Lee, Seonki Hong, Gyuhyung Jin, Minhee Kim, Kook In Park, Haeshin Lee, Jae-Hyung Jang
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 6 Issue 11 Pg. 8288-94 (Jun 11 2014) ISSN: 1944-8252 [Electronic] United States
• PMID: 24827581 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dopamine
• Norepinephrine

Topics

• Cell Line
• Dependovirus (genetics)
• Dopamine (administration & dosage)
• Gene Transfer Techniques
• Humans
• Neural Stem Cells (virology)
• Norepinephrine (administration & dosage)