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Covalently tethering siRNA to hydrogels for localized, controlled release and gene silencing.


ABSTRACT: Small interfering RNA (siRNA) has found many applications in tissue regeneration and disease therapeutics. Effective and localized siRNA delivery remains challenging, reducing its therapeutic potential. Here, we report a strategy to control and prolong siRNA release by directly tethering transfection-capable siRNA to photocrosslinked dextran hydrogels. siRNA release is governed via the hydrolytic degradation of ester and/or disulfide linkages between the siRNA and hydrogels, which is independent of hydrogel degradation rate. The released siRNA is shown to be bioactive by inhibiting protein expression in green fluorescent protein-expressing HeLa cells without the need of a transfection agent. This strategy provides an excellent platform for controlling nucleic acid delivery through covalent bonds with a biomaterial and regulating cellular gene expression, which has promising potential in many biomedical applications.

SUBMITTER: Nguyen MK 

PROVIDER: S-EPMC6713499 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Covalently tethering siRNA to hydrogels for localized, controlled release and gene silencing.

Nguyen Minh Khanh MK   Huynh Cong Truc CT   Gilewski Alex A   Wilner Samantha E SE   Maier Keith E KE   Kwon Nicholas N   Levy Mathew M   Alsberg Eben E  

Science advances 20190828 8


Small interfering RNA (siRNA) has found many applications in tissue regeneration and disease therapeutics. Effective and localized siRNA delivery remains challenging, reducing its therapeutic potential. Here, we report a strategy to control and prolong siRNA release by directly tethering transfection-capable siRNA to photocrosslinked dextran hydrogels. siRNA release is governed via the hydrolytic degradation of ester and/or disulfide linkages between the siRNA and hydrogels, which is independent  ...[more]

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