Covalently tethering siRNA to hydrogels for localized, controlled release and gene silencing
| Autor: | Eben Alsberg, Mathew Levy, Keith E. Maier, Cong Truc Huynh, Samantha E. Wilner, Alex Gilewski, Nicholas Kwon, Minh Khanh Nguyen |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Small interfering RNA
Green Fluorescent Proteins Materials Science Biocompatible Materials 02 engineering and technology Transfection 010402 general chemistry complex mixtures Biochemistry 01 natural sciences Cell Line Tumor Gene expression Humans Gene silencing Gene Silencing RNA Small Interfering Research Articles Multidisciplinary Chemistry technology industry and agriculture SciAdv r-articles RNA Hydrogels 021001 nanoscience & nanotechnology Controlled release 0104 chemical sciences Cell biology Cell culture Delayed-Action Preparations Self-healing hydrogels RNA Interference 0210 nano-technology HeLa Cells Research Article |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| DOI: | 10.1126/sciadv.aax0801 |
| Popis: | Covalently tethering RNA to hydrogel provides the prolonged presentation of RNA for locally sustained cellular gene silencing. 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. |
| Databáze: | OpenAIRE |
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