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Intracellular trafficking of hybrid gene delivery vectors.
- Source :
-
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2015 Jun 10; Vol. 207, pp. 120-30. Date of Electronic Publication: 2015 Apr 14. - Publication Year :
- 2015
-
Abstract
- Viral and non-viral gene delivery vectors are in development for human gene therapy, but both exhibit disadvantages such as inadequate efficiency, lack of cell-specific targeting or safety concerns. We have recently reported the design of hybrid delivery vectors combining retrovirus-like particles with synthetic polymers or lipids that are efficient, provide sustained gene expression and are more stable compared to native retroviruses. To guide further development of this promising class of gene delivery vectors, we have investigated their mechanisms of intracellular trafficking. Moloney murine leukemia virus-like particles (M-VLPs) were complexed with chitosan (Chi) or liposomes (Lip) comprising DOTAP, DOPE and cholesterol to form the hybrid vectors (Chi/M-VLPs and Lip/M-VLPs, respectively). Transfection efficiency and cellular internalization of the vectors were quantified in the presence of a panel of inhibitors of various endocytic pathways. Intracellular transport and trafficking kinetics of the hybrid vectors were dependent on the synthetic component and used a combination of clathrin- and caveolar-dependent endocytosis and macropinocytosis. Chi/M-VLPs were slower to transfect compared to Lip/M-VLPs due to the delayed detachment of the synthetic component. The synthetic component of hybrid gene delivery vectors plays a significant role in their cellular interactions and processing and is a key parameter for the design of more efficient gene delivery vehicles.<br /> (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Subjects :
- Blood Proteins metabolism
Caveolae metabolism
Chitosan chemistry
Cholesterol chemistry
Clathrin-Coated Vesicles metabolism
Fatty Acids, Monounsaturated chemistry
HEK293 Cells
HeLa Cells
Humans
Kinetics
Liposomes
Microscopy, Confocal
Moloney murine leukemia virus genetics
Phosphatidylethanolamines chemistry
Pinocytosis
Quaternary Ammonium Compounds chemistry
Temperature
Virion genetics
Virion metabolism
Chitosan metabolism
Cholesterol metabolism
Endocytosis drug effects
Fatty Acids, Monounsaturated metabolism
Genetic Vectors
Moloney murine leukemia virus metabolism
Phosphatidylethanolamines metabolism
Quaternary Ammonium Compounds metabolism
Transfection methods
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4995
- Volume :
- 207
- Database :
- MEDLINE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Publication Type :
- Academic Journal
- Accession number :
- 25883029
- Full Text :
- https://doi.org/10.1016/j.jconrel.2015.04.015