Sticky "delivering-from" strategies using viral vectors for efficient human neural stem cell infection by bioinspired catecholamines.
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.
Department of Chemical and Biomolecular Engineering, Yonsei University , 50 Yonsei-Ro, Seoul 120-749, Korea.
Eunmi
E
Kim
Slgirim
S
Lee
Seonki
S
Hong
Gyuhyung
G
Jin
Minhee
M
Kim
Kook In
KI
Park
Haeshin
H
Lee
Jae-Hyung
JH
Jang
D002460:Cell Line; D000229:Dependovirus / Q000235:genetics*; D004298:Dopamine / Q000008:administration & dosage*; D018014:Gene Transfer Techniques; D006801:Humans; D058953:Neural Stem Cells / Q000821:virology*; D009638:Norepinephrine / Q000008:administration & dosage*
D004298:Dopamine; D009638:Norepinephrine