Journal
BIOMATERIALS
Volume 178, Issue -, Pages 720-727Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2018.02.007
Keywords
siRNA delivery; Steroid; Intercalate; Transmembrane; Endocytosis; Non-covalent
Funding
- NIH [R01CA140295]
- Department of Bioengineering
- Office of Research at University of Washington
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Short interfering RNA (siRNA) has broad applications in biology and medicine, and holds tremendous potential to become a new class of therapeutics for many diseases. As a highly anionic macrobiomolecule, its cytosolic delivery, however, has been a major roadblock in translation. Here, we report the development of small, bifunctional chemical tags capable of transporting siRNA directly into the cytosol. The bifunctional tags consist of a siRNA-binding moiety that interacts with siRNA non-covalently, and a steroid domain that readily fuses with the mammalian cell membrane. In contrast to the conventional covalently conjugated siRNA-steroid that enters cells largely via endocytosis which substantially limits siRNA bioavailability, the non-covalently tagged siRNA is cell membrane-permeant, avoiding the endocytic pathway. This new methodology enables effective RNA interference (RNAi) without the need of cationic transfection or endosomolytic agents, opening a new avenue for intracellular delivery of native biologics. (C) 2018 Elsevier Ltd. All rights reserved.
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