2 research outputs found
Integration of Adeno-Associated Virus-Derived Peptides into Nonviral Vectors to Synergistically Enhance Cellular Transfection
This study describes a simple, versatile
approach for developing
a nonviral gene carrier by adopting the highly efficient gene delivery
properties of the adeno-associated virus (AAV). Specific viral peptides
(r3.45_hepBD) extracted from AAV r3.45, which directly evolved to
improve gene delivery capabilities in many cell types, were conjugated
onto branched polyethylenimine (PEI) to form hybrid gene carriers.
AAV r3.45 carries a sequence insertion (LATQVGQKTA; r3.45) within
the heparin-binding domain (LQRGNRQA; hepBD), which ultimately comprises
a novel sequence (LQRGNLATQVGQKTARQA; r3.45_hepBD) on the capsid.
This sequence is hypothesized to be a crucial cue to enhance gene
delivery efficiency. Consequently, the intimate interactions of the
conjugated r3.45_hepBD with the glycosaminoglycans, including chondroitin
sulfate, resulted in significantly enhanced cellular transfection
of DNA/PEI-r3.45_hepBD complexes. The successful establishment of
a nonviral system that is built with novel peptides will provide a
powerful means for developing a substantial number of gene therapy
applications
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