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배서현Seo-Hyeon Bae

가톨릭대학교

Bioact. Mater., 2024 May 14:38:486-498 | https://doi.org/10.1016/j.bioactmat.2024.05.012 A lipid nanoparticle platform incorporating trehalose glycolipid for exceptional mRNA vaccine safety

Seo-Hyeon Bae ^a,b,1, Soyeon Yoo^c,1, Jisun Lee ^a,1, Hyo-Jung Park ^a,b,1, Sung Pil Kwon ^c, Harin Jin ^d,e, Sang-In Park ^f, Yu-Sun Lee^a,b, Yoo-Jin Bang ^a,b, Gahyun Roh ^a,b, Seonghyun Lee ^a,b, Sue Bean Youn ^a,b, In Woo Kim ^h, Ho Rim Oh ^h, Ashraf K. El-Damasy ^c, Gyochang Keum ^c, Hojun Kim ^d,e, Hyewon Youn ^h,i, Jae-Hwan Nam ^a,b, Eun-Kyoung Bang ^c,g

^aDepartment of Medical and Biological Sciences, The Catholic University of Korea, Gyeonggi-do, Bucheon, Republic of Korea

^bBK Four Department of Biotechnology, The Catholic University of Korea, Gyeonggi-do, Bucheon, Republic of Korea

^cCenter for Brain Technology, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea

^dCenter for Advanced Biomolecular Recognition, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea

^eDivision of Bio-Medical Science and Technology, KIST School, University of Science and Technology (UST), Seoul, Republic of Korea

^fSML Biopharm, Gwangmyeong, 14353, Republic of Korea

^gKHU-KIST Department of Converging Science and Technology, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea

^hCancer Research Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea

ⁱDepartment of Nuclear Medicine, Cancer Imaging Center, Seoul National University Hospital, Seoul, 03080, Republic of Korea

¹These authors equally contributed to this work.

Corresponding authors: Hyewon Youn, Jae-Hwan Nam, Eun-Kyoung Bang

Abstract

The rapid development of messenger RNA (mRNA) vaccines formulated with lipid nanoparticles (LNPs) has contributed to control of the COVID-19 pandemic. However, mRNA vaccines have raised concerns about their potential toxicity and clinical safety, including side effects, such as myocarditis, anaphylaxis, and pericarditis. In this study, we investigated the potential of trehalose glycolipids-containing LNP (LNP S050L) to reduce the risks associated with ionizable lipids. Trehalose glycolipids can form hydrogen bonds with polar biomolecules, allowing the formation of a stable LNP structure by replacing half of the ionizable lipids. The efficacy and safety of LNP S050L were evaluated by encapsulating the mRNA encoding the luciferase reporter gene and measuring gene expression and organ toxicity, respectively. Furthermore, mice immunized with an LNP S050L-formulated mRNA vaccine expressing influenza hemagglutinin exhibited a significant reduction in organ toxicity, including in the heart, spleen, and liver, while sustaining gene expression and immune efficiency, compared to conventional LNPs (Con-LNPs). Our findings suggest that LNP S050L, a trehalose glycolipid-based LNP, could facilitate the development of safe mRNA vaccines with improved clinical safety.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-06-13)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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