서원효 (이화여자대학교)

한빛사논문

조회123

이화여자대학교

CV File 237 kb

J. Control. Release, Aug 22 2024, 374 S0168-3659(24)00551-0 | https://doi.org/10.1016/j.jconrel.2024.08.012 Engineered lipid nanoparticles enable therapeutic gene silencing of GTSE1 for the treatment of liver fibrosis

Michaela Jeong ^a,1, Sumin Shin ^a,1, Gyeongseok Lee ^a, Yeji Lee ^a, Seo Bhin Park ^a, Jisoo Kang ^a, Young-Sun Lee ^b, Wonhyo Seo ^a, Hyukjin Lee ^a

^aCollege of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea

^bDepartment of Internal Medicine, Korea University Medical Center, Seoul 08308, Republic of Korea

¹These authors contributed equally

Corresponding authors : Wonhyo Seo, Hyukjin Lee

Abstract

Liver fibrosis is characterized by abnormal accumulation of extracellular matrix proteins, disrupting normal liver function. Despite its significant health impact, effective treatments remain limited. Here, we present the development of engineered lipid nanoparticles (LNPs) for targeted RNA therapeutic delivery in the liver. We investigated the therapeutic potential of modulating the G2 and S-phase expressed 1 (GTSE1) protein for treating liver fibrosis. Through screening, we identified P138Y LNP as a potent candidate with superior delivery efficiency and lower toxicity. Using these engineered LNPs, we successfully delivered siGTSE1 to hepatocytes, significantly reducing collagen accumulation and restoring liver function in a fibrosis animal model. Additionally, GTSE1 downregulation altered miRNA expression and upregulated hepatocyte nuclear factor 4 alpha (HNF4α). These findings suggest that therapeutic gene silencing of GTSE1 is a promising strategy for treating liver fibrosis by regenerating liver phenotypes and functions.

논문정보

형식Research article
게재일2024년 08월 (BRIC 등록일 2024-09-04)
연구진국내 연구진
분야 의약학 > 약학

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