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Functional Delivery of Lipid-Conjugated siRNA by Extracellular Vesicles.
- Source :
-
Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2017 Jul 05; Vol. 25 (7), pp. 1580-1587. Date of Electronic Publication: 2017 Apr 06. - Publication Year :
- 2017
-
Abstract
- Extracellular vesicles (EVs) are cell-derived, membranous nanoparticles that mediate intercellular communication by transferring biomolecules, including proteins and RNA, between cells. As a result of their suggested natural capability to functionally deliver RNA, EVs may be harnessed as therapeutic RNA carriers. One major limitation for their translation to therapeutic use is the lack of an efficient, robust, and scalable method to load EVs with RNA molecules of interest. Here, we evaluated and optimized methods to load EVs with cholesterol-conjugated small interfering RNAs (cc-siRNAs) by systematic evaluation of the influence of key parameters, including incubation time, volume, temperature, and EV:cc-siRNA ratio. EV loading under conditions that resulted in the highest siRNA retention percentage, incubating 15 molecules of cc-siRNA per EV at 37°C for 1 hr in 100 μL, facilitated concentration-dependent silencing of human antigen R (HuR), a therapeutic target in cancer, in EV-treated cells. These results may accelerate the development of EV-based therapeutics.<br /> (Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Base Sequence
Biological Transport
Cell Line
Cell Line, Tumor
Cholesterol metabolism
ELAV-Like Protein 1 genetics
ELAV-Like Protein 1 metabolism
Extracellular Vesicles chemistry
Fibroblasts cytology
Fibroblasts metabolism
Gene Expression
HEK293 Cells
Humans
Mice
Neoplasm Proteins genetics
Neoplasm Proteins metabolism
Neurons metabolism
Neurons pathology
Permeability
RNA, Small Interfering genetics
Temperature
Cholesterol chemistry
Drug Delivery Systems
ELAV-Like Protein 1 antagonists & inhibitors
Extracellular Vesicles metabolism
Neoplasm Proteins antagonists & inhibitors
RNA, Small Interfering metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1525-0024
- Volume :
- 25
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Molecular therapy : the journal of the American Society of Gene Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 28392161
- Full Text :
- https://doi.org/10.1016/j.ymthe.2017.03.021