Journal
MOLECULAR THERAPY
Volume 26, Issue 6, Pages 1520-1528Publisher
CELL PRESS
DOI: 10.1016/j.ymthe.2018.03.019
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Funding
- NIH UH3 grant [TR 000888 05]
- NIH [RO1GM10880304, RO1NS10402201, S10 OD020012]
- CHDI Foundation [A-6119, JSC A6367]
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Small extracellular vesicles (sEVs) show promise as natural nano-devices for delivery of therapeutic RNA, but efficient loading of therapeutic RNA remains a challenge. We have recently shown that the attachment of cholesterol to small interfering RNAs (siRNAs) enables efficient and productive loading into sEVs. Here, we systematically explore the ability of lipid conjugates-fatty acids, sterols, and vitamins-to load siRNAs into sEVs and support gene silencing in primary neurons. Hydrophobicity of the conjugated siRNAs defined loading efficiency and the silencing activity of siRNA-sEVs complexes. Vitamin-E-conjugated siRNA supported the best loading into sEVs and productive RNA delivery to neurons.
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