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조회464

유소연Soyeon Yoo

한국과학기술연구원

Adv. Healthc. Mater., Nov 06 2024, | https://doi.org/10.1002/adhm.202403366 Novel Less Toxic, Lymphoid Tissue-Targeted Lipid Nanoparticles Containing a Vitamin B5-Derived Ionizable Lipid for mRNA Vaccine Delivery

Soyeon Yoo¹, Muhammad Faisal^1,2, Seo-Hyeon Bae^3,4, Kounghwa Youn^1,5, Hyo-Jung Park^3,4, Sung Pil Kwon¹, Il Kwon Hwang^1,6, Jisun Lee³, Hyeong Jun Kim⁷, Jae-Hwan Nam^3,4,8, Gyochang Keum^1,2, Eun-Kyoung Bang^1,5,6

¹Brain Technology Research Center, Brain Science Research Division, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul, 02792, Republic of Korea.

²Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology (UST), Seoul, 02792, Republic of Korea.

³Department of Medical and Biological Sciences, The Catholic University of Korea, 43 Jibong-ro, Bucheon, Gyeonggi-do, 14662, Republic of Korea.

⁴BK21 four Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Bucheon, Gyeonggi-do, 14662, South Korea.

⁵KHU-KIST Department of Converging Science and Technology, Kyung Hee University, 7-13 Kyungheedae-ro 6-gil, Dongdaemun-gu, Seoul, 02447, Republic of Korea.

⁶Department of Chemical and Biological Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea.

⁷Medicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul, 02792, Republic of Korea.

⁸SML Biopharm, Gwangmyeong Station M Cluster, 17 Deokan-ro 104beon-gil, Gwangmyeong-si, Gyeonggi-do, 14353, Republic of Korea.

S.Y., M.F., S.-H.B., K.Y. and H.-J. P. contributed equally to the work in thispaper.

Corresponding Authors: Jae-Hwan Nam, Gyochang Keum, Eun-Kyoung Bang

Abstract

Following their approval by the Food and Drug Administration, lipid nanoparticles (LNPs) have emerged as promising tools for delivering mRNA vaccines and therapeutics. Ionizable lipids are among the essential components of LNPs, as they play crucial roles in encapsulating mRNA and facilitating its release into the cytosol. In this study, 17 innovative ionizable lipids using vitamin B5 are designed as the core structure, aiming to reduce toxicity, to maintain vaccine efficiency, and to ensure synthetic feasibility. The top-performing LNP in terms of mRNA vaccine delivery in the mouse model is LNP 5097, which is generated by incorporating ionizable lipid I97. mRNA⊂LNP 5097 demonstrates favorable structural and physicochemical properties, high mRNA transfection efficiency, and long-term stability. Moreover, mRNA⊂LNP 5097 specifically delivers the mRNA to the spleen and lymph nodes in model mice, induces balanced Th1/Th2 immune responses, and elicits the production of high levels of neutralizing antibodies with low toxicity. The findings here suggest the high utility of LNP 5097, which includes novel vitamin B5-derived ionizable lipids with reduced toxicity, in mRNA vaccine research for both infectious diseases and cancer.

논문정보

형식Research article
게재일2024년 11월 (BRIC 등록일 2024-11-07)
연구진국내 연구진
분야 바이오·의료융합 > 바이오소재

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