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ACS Nano, Feb 05 2025, | https://doi.org/10.1021/acsnano.4c16562
Apolipoprotein Fusion Enables Spontaneous Functionalization of mRNA Lipid Nanoparticles with Antibody for Targeted Cancer Therapy
Wonbeom Park 1, Jiwoong Choi 2, Jaehyeon Hwang 1, Suhyun Kim 1, Yelee Kim 2,3, Man Kyu Shim 2, Wooram Park 1, Seokhyeon Yu 4, Sangwon Jung 4, Yoosoo Yang 2,5, Dae-Hyuk Kweon 1
1Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea.
2Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.
3Department of Life Sciences, Korea University, Seoul 02841, Republic of Korea.
4Research Center, MVRIX, Anyang 14058, Republic of Korea.
5Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea.
W.P. and J.C. contributed equally to this work.
Corresponding Authors: Yoosoo Yang, Dae-Hyuk Kweon
1Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea.
2Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.
3Department of Life Sciences, Korea University, Seoul 02841, Republic of Korea.
4Research Center, MVRIX, Anyang 14058, Republic of Korea.
5Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea.
W.P. and J.C. contributed equally to this work.
Corresponding Authors: Yoosoo Yang, Dae-Hyuk Kweon
Abstract
The mRNA-lipid nanoparticles (mRNA@LNPs) offer a novel opportunity to treat targets previously considered undruggable. Although antibody conjugation is crucial for enhancing the specificity, delivery efficiency, and minimizing the toxicity of mRNA therapeutics, current chemical conjugation methods are complex and produce heterogeneous particles with misoriented antibodies. In this work, we introduce a chemical-free approach to functionalize mRNA@LNPs with antibodies, mimicking protein corona formation for targeted mRNA delivery. By fusing apolipoprotein to the Fc domain of a targeting antibody, we enabled the antibody to spontaneously display on the surface of mRNA@LNPs without altering the existing LNP process or employing complex chemical conjugation techniques. We demonstrated precise protein expression using trastuzumab-bound mRNA@LNPs, facilitating specific mRNA expression in HER2-positive cancer cells. mRNA was efficiently delivered to the tumor site after intravenous administration. While the control LNPs lacking targeting antibodies caused acute liver toxicity, trastuzumab-displayed LNPs showed no systemic toxicity. The tumor-specific delivery of p53 tumor suppressor mRNA led to the complete regression of cancer cells. Thus, apolipoprotein fusion enables a straightforward and scalable production of antibody-functionalized mRNA@LNPs, offering significant therapeutic potential in gene therapy.
논문정보
- Research article
- 2025년 02월 (BRIC 등록일 2025-02-06)
- 국내 연구진
- 생명과학 > 생물공학
관련 보도자료
지질나노입자 표적 전달 기술 개발
성균관대학교 융합생명공학과 권대혁 교수 연구팀이 한국과학기술연구원 양유수 박사, 바이오 기업 엠브릭스㈜와 공동으로 mRNA를 특정 세포에 효과적으로 전달할 수 있는 혁신적인 기술을 개발했다. 이번 연구는 차세대 유전자 치료와 항암 치료의 발전을 앞당길 핵심 기술로 주목받고 있다. mRNA를 세포에 전달하는 지질나노입자(LNP) 기술은 코로나19 백신으로 큰 성공을 거두었지만, 특정 세포에 정확히 전달하는 데 한계가 있었다. 이로 인해 활용 범위가 제한되며, 예상치 못한 부작용이 발생할 우려가 있었다.
- Bio통신원
- 2025. 02. 24
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