mt0c00351_si_001.pdf (395.95 kB)
A Versatile Adeno-Associated Viral Vector Cross-Linking Platform Capable of Tuning Cellular Tropisms and Simultaneously Inducing Solid-Phase Gene Delivery
journal contribution
posted on 2020-08-05, 16:08 authored by Seungju Yoo, Byunguk Kang, Seokmin Oh, Yunha Kim, Jae-Hyung JangDeveloping gene carriers
with improved affinities for target cells
and the simultaneous diversification of their delivery modes will
be pivotal for upgrading gene therapy technologies. In this study,
a simple and versatile adeno-associated virus (AAV) conjugation platform
using the cross-linker 3,3′-dithiobis(sulfosuccinimidyl propionate)
(DTSSP) is proposed. Depending on the quantity of the DTSSP molecules,
the AAV-DTSSP complexes could either be linked with the relevant biomolecules
for altering cellular tropisms or further form a self-assembled AAV-DTSSP
pellet capable of mimicking a polymeric gene delivery system. At lower
quantities of DTSSP, the AAV-DTSSP complexes were conjugated with
aminated l-fucose molecules, whose levels are typically upregulated
in pancreatic cancer cells, resulting in enhanced gene delivery efficiencies
in pancreatic cancer cells. At higher concentrations of DTSSP, visible
solid forms of the AAV-DTSSP pellets were formed, and the AAV pellets
demonstrated the capability to induce a localized, sustained gene
expression pattern comparable to that of conventional biomaterial-based
approaches. Thus, a multipurpose AAV cross-linking platform, which
can enable AAV vector systems that are capable of altering cellular
tropisms and simultaneously inducing solid-phase delivery, will provide
crucial insights into vector design for further upgrading of gene
delivery technologies.
History
Usage metrics
Categories
Keywords
Tuning Cellular Tropismsgene delivery technologiespancreatic cancer cellsgene delivery systemVersatile Adeno-Associated Viral Ve...AAV-DTSSP complexesInducing Solid-Phase Gene Deliverygene expression patternAAV cross-linking platformself-assembled AAV-DTSSP pelletaminated l-fucose moleculesAAV vector systemsgene delivery efficienciesgene therapy technologies
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC