Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/146638
Title: Positive-charge tuned gelatin hydrogel-siSPARC injectable for siRNA anti-scarring therapy in post glaucoma filtration surgery
Authors: Chun, Yong Yao
Yap, Zhu Li
Seet, Li Fong
Chan, Hiok Hong
Toh, Li Zhen
Chu, Stephanie W. L.
Lee, Ying Shi
Wong, Tina T.
Tan, Timothy Thatt Yang
Keywords: Engineering::Chemical engineering
Issue Date: 2021
Source: Chun, Y. Y., Yap, Z. L., Seet, L. F., Chan, H. H., Toh, L. Z., Chu, S. W. L., . . . Tan, T. T. Y. (2021). Positive-charge tuned gelatin hydrogel-siSPARC injectable for siRNA anti-scarring therapy in post glaucoma filtration surgery. Scientific Reports, 11(1), 1470-. doi:10.1038/s41598-020-80542-4
Project: M4081851
NGF-2019-07-004
NMRC/TCR/008-SERI/2013
NMRC/CG/015/2013
Journal: Scientific Reports
Abstract: Small interfering RNA (siRNA) therapy is a promising epigenetic silencing strategy. However, its widespread adoption has been severely impeded by its ineffective delivery into the cellular environment. Here, a biocompatible injectable gelatin-based hydrogel with positive-charge tuned surface charge is presented as an effective platform for siRNA protection and delivery. We demonstrate a two-step synthesis of a gelatin-tyramine (Gtn-Tyr) hydrogel with simultaneous charge tunability and crosslinking ability. We discuss how different physiochemical properties of the hydrogel interact with siSPARC (siRNA for secreted protein, acidic and rich in cysteine), and study the positive-charge tuned gelatin hydrogel as an effective delivery platform for siSPARC in anti-fibrotic treatment. Through in vitro studies using mouse tenon fibroblasts, the positive-charge tuned Gtn-Tyr hydrogel shows sustained siSPARC cellular internalization and effective SPARC silencing with excellent biocompatibility. Similarly, the same hydrogel platform delivering siSPARC in an in vivo assessment employing a rabbit model shows an effective reduction in subconjunctival scarring in post glaucoma filtration surgery, and is non-cytotoxic compared to a commonly used anti-scarring agent, mitomycin-C. Overall, the current siRNA delivery strategy involving the positive-charge tuned gelatin hydrogel shows effective delivery of gene silencing siSPARC for anti-fibrotic treatment. The current charge tunable hydrogel delivery system is simple to fabricate and highly scalable. We believe this delivery platform has strong translational potential for effective siRNA delivery and epigenetic silencing therapy.
URI: https://hdl.handle.net/10356/146638
ISSN: 2045-2322
DOI: 10.1038/s41598-020-80542-4
Rights: © 2021 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SCBE Journal Articles

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