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Chem. Eng. J., Volume 505, 1 February 2025, 159532 | https://doi.org/10.1016/j.cej.2025.159532
One-pot modular nanogel platform utilizing phenolic gelatin-polyethyleneimine for small RNA delivery
Kyoungmin Park a, Jie Zheng a,1, Jeong-Eun Yoo c, Jonggun Kim c, In-Yong Kim a,b, Seungkwon You a,b
aDepartment of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea
bInstitute of Animal Molecular Biotechnology, Korea University, Seoul 02841, Republic of Korea
cInstitute of Regenerative Medicine, SL Therapeutics Inc., Seoul 02841, Republic of Korea
1Present address: Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325000, China.
Corresponding authors: In-Yong Kim, Seungkwon You
aDepartment of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea
bInstitute of Animal Molecular Biotechnology, Korea University, Seoul 02841, Republic of Korea
cInstitute of Regenerative Medicine, SL Therapeutics Inc., Seoul 02841, Republic of Korea
1Present address: Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325000, China.
Corresponding authors: In-Yong Kim, Seungkwon You
Abstract
With the vast potential of RNA drugs widely recognized, nanoparticles have emerged as a promising tool for their bench-to-bedside translation in a broad range of clinical settings. However, despite the development of thousands of polymers for small RNA (sRNA) delivery, their clinical translatability remains limited. Here, we describe a modular nanogel platform, sRNA-moduGels, that can be administered immediately after simple, one-pot preparation within 5 mins, regardless of expertise or specialized equipment. sRNA-moduGels were prepared through high-shear granulation of RNA/polymer agglomerates, induced by agitated fluid mixing and electrostatic interactions between sRNA and the cross-linkable precursor material, phenolic gelatin-branched polyethyleneimine (phGel-PEI). The resulting sRNA-moduGels were characterized for size, surface charge, loading efficiency, stability, release profile, and resistance to RNase degradation. Extensive in vitro evaluations, including cytotoxicity, intracellular uptake, and gene silencing efficacy, were conducted across various dosages, cell types, and mi/siRNAs. Additionally, organ-specific distribution and safety were also assessed in vivo. This study provides proof of concept for the flexible application of sRNA-moduGels as an RNA delivery platform and potentially serves as a prototype for advancing the translation of RNA discoveries, broadening their applicability through further engineering of ready-to-use nanogel materials.
논문정보
- Research article
- 2025년 02월 (BRIC 등록일 2025-02-01)
- 국내 연구진
- 바이오·의료융합 > 바이오소재
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