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한빛사논문
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ACS Nano, Aug 22 2024, | https://doi.org/10.1021/acsnano.4c05653
Inhalable mRNA Nanoparticle with Enhanced Nebulization Stability and Pulmonary Microenvironment Infiltration
Mincheol Jang 1, Kyunghwan Yeom 1, Junhee Han 1, Erinn Fagan 1, Ji-Ho Park 1
1Department of Bio and Brain Engineering and KAIST Institute for Health Science and Technology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
Corresponding Author : Ji-Ho Park
Abstract
The delivery of mRNA into the lungs is the key to solving infectious and intractable diseases that frequently occur in the lungs. Since inhalation using a nebulizer is the most promising method for mRNA delivery into the lungs, there have been many attempts toward adapting lipid nanoparticles for mRNA inhalation. However, conventional lipid nanoparticles, which have shown great effectiveness for systemic delivery of mRNA and intramuscular vaccination, are not effective for pulmonary delivery due to their structural instability during nebulization and their inability to adapt to the pulmonary microenvironment. To address these issues, we developed an ionizable liposome-mRNA lipocomplex (iLPX). iLPX has a highly ordered lipid bilayer structure, which increases stability during nebulization, and its poly(ethylene glycol)-free composition allows it to infiltrate the low serum environment and the pulmonary surfactant layer in the lungs. We selected an inhalation-optimized iLPX (IH-iLPX) using a multistep screening procedure that mimics the pulmonary delivery process of inhaled nanoparticles. The IH-iLPX showed a higher transfection efficiency in the lungs compared to conventional lipid nanoparticles after inhalation with no observed toxicity
in vivo. Furthermore, analysis of lung distribution revealed even protein expression in the deep lungs, with effective delivery to epithelial cells. This study provides insights into the challenges and solutions related to the development of inhaled mRNA pulmonary therapeutics.
논문정보
- Research article
- 2024년 08월 (BRIC 등록일 2024-08-29)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
관련 보도자료
기존보다 26배 효과적인 폐질환 흡입치료 가능
코로나19의 전 세계적 유행 이후, 폐 등 호흡기 질병에 대비하기 위한 mRNA 백신 및 치료제는 차세대 치료제로 주목받고 있다. 하지만 기존 mRNA 백신용 전달체가 가지고 있는 한계점을 극복하고 KAIST 연구진이 호흡기 바이러스 및 난치성 폐질환의 mRNA 흡입 치료를 가능케 하며 유전자 폐 치료 연구의 근간이 될 연구에 성공했다. KAIST(총장 이광형)는 바이오및뇌공학과 박지호 교수 연구팀이 유전자 폐 치료에 최적화된 나노 전달체를 개발했다고 7일 밝혔다.
- Bio통신원
- 2024. 10. 07
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