Enhance transgene responses through improving cellular uptake and intracellular trafficking by bio-inspired non-viral vectors

Autor: Si-Yuan Zhou, Yi-Yang Jia, Ya-Xuan Zhang, Chen Li, Jing-Liang Xu, Wei He, Bang-Le Zhang, Wang Wei, Xi-Xi Ma
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Calcium Phosphates
Cell Membrane Permeability
Genetic enhancement
Pharmaceutical Science
Medicine (miscellaneous)
02 engineering and technology
Applied Microbiology and Biotechnology
Transduction
Genetic
Mannitol
Vector (molecular biology)
Transgenes
0303 health sciences
Chemistry
Gene Transfer Techniques
021001 nanoscience & nanotechnology
Cell biology
medicine.anatomical_structure
lcsh:R855-855.5
Molecular Medicine
0210 nano-technology
Intracellular
Signal Transduction
Gene Expression Regulation
Viral
lcsh:Medical technology
Endosome
Surface Properties
Transgene
Cellular uptake pathway
lcsh:Biotechnology
Genetic Vectors
Biomedical Engineering
Bioengineering
Endosomes
Caveolae
Transfection
Viral vector
Cell Line
03 medical and health sciences
Lysosome
lcsh:TP248.13-248.65
medicine
Humans
Gene
030304 developmental biology
Research
Genetic Therapy
Clathrin
Nanoparticles
Non-viral vectors
Lysosomes
Intracellular trafficking
Zdroj: Journal of Nanobiotechnology, Vol 18, Iss 1, Pp 1-14 (2020)
Journal of Nanobiotechnology
ISSN: 1477-3155
Popis: Background Gene therapy remains a significant challenge due to lots of barriers limiting the genetic manipulation technologies. As for non-viral delivery vectors, they often suffer insufficient performance due to inadequate cellular uptake and gene degradation in endosome or lysosome. The importance of overcoming these conserved intracellular barriers is increasing as the delivery of genetic cargo. Results A surface-functionalized non-viral vector involving the biomimetic mannitol moiety is initiated, which can control the cellular uptake and promote the caveolae-mediated pathway and intracellular trafficking, thus avoiding acidic and enzymatic lysosomal degradation of loaded gene internalized by clathrin-mediated pathway. Different degrees of mannitol moiety are anchored onto the surface of the nanoparticles to form bio-inspired non-viral vectors and CaP-MA-40 exhibits remarkably high stability, negligible toxicity, and significantly enhanced transgene expression both in vitro and in vivo. Conclusions This strategy highlights a paradigmatic approach to construct vectors that need precise intracellular delivery for innovative applications.
Databáze: OpenAIRE
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