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J. Control. Release, Apr 12 2025, S0168-3659(25)00355-4 | https://doi.org/10.1016/j.jconrel.2025.113735 The therapeutic potential of mRNA-encoded SFTSV human monoclonal antibody encapsulated lipid nanoparticle in vivo

Soo-Yeon Lee ^a,b,1, Yebeen Lee ^c,1, Eun Young Oh ^d,1, Jisun Lee^a,1, Jae-Yong Kim ^e,1, Sang-In Park^f,1, Hyo-Jung Park ^a,b,1, So Hyun Park ^d, Eun-Jin Choi^a,b, Dahyeon Ha ^a,b, Ayoung Oh ^a,b, Ayeon Kim ^a,b, Hyo-Jin Ro ^c, Yoo-Jin Bang ^e, Hye Won Kwak ^e, Hyeong-Jun Park ^e, Do-Hyung Kim ^e, Daegeun Kim ^e, Sang-Myeong Lee ^d,g,h, Nam-Hyok Cho^c,g,h, Jae-Hwan Nam ^a,b

^aThe Catholic University of Korea, Bucheon, Republic of Korea
^bBK21 plus Department of Biotechnology, The Catholic University of Korea, Gyeonggi-do, Bucheon, Republic of Korea
^cDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea
^dCollege of Veterinary Medicine, Chungbuk National University, Cheongju, -si, Chungcheongbuk-do, Republic of Korea
^eSML Biopharm, Gwangmyeong, Republic of Korea
^fDepartment of Biomedical Laboratory Science, Daegu Haany University, Gyeongsan 38610, Republic of Korea
^gDepartment of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
^hSeoul National University Bundang Hospital, Seongnam, Gyeonggi-do 13620, Republic of Korea

¹These authors contributed equally to this work.
Correspondence to: Sang-Myeong Lee, Nam-Hyok Cho, Jae-Hwan Nam

Abstract

Severe fever with thrombocytopenia syndrome (SFTS), caused by the SFTS virus (SFTSV), has emerged as a significant public health concern in East Asia since 2009. The high mortality rate of SFTS underscores the urgent need for effective preventive and therapeutic interventions. Although a Gn-specific human monoclonal antibody, Ab10, herein referred to as the protein S/A-TEN, has been previously reported, its development has been hindered by the economic challenges and low yields of large-scale production. To address this limitation, we developed an mRNA encapsulated lipid nanoparticle to produce SFTSV-specific human mAbs (mRNA S/A-TEN). This novel approach facilitates small-scale production, potentially enabling direct human application. The mRNA S/A-TEN antibody obtained from the injected-mouse serum showed high neutralizing antibody titers. Furthermore, we found that injecting the mRNA S/A-TEN antibody into mice that were infected with lethal SFTSV resulted in 100 % survival and assisted in a rapid recovery from organ failure. This study provides the first evidence that an mRNA-encoded SFTSV-specific human mAb can provide effective therapeutic protection against SFTSV infection, offering a promising therapeutic approach for the treatment of human SFTS.

논문정보

형식Research article
게재일2025년 04월 (BRIC 등록일 2025-04-15)
연구진국내 연구진
분야 의약학 > 감염의학

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