한빛사논문
- 조회654
Minjeong Kim1,2, Michaela Jeong1, Gyeongseok Lee1, Yeji Lee1, Jeongeun Park1, Hyein Jung1, Seongeun Im1, Joo-Sung Yang3, Kyungjin Kim3, Hyukjin Lee1
1College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea
2Department of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas,Texas, USA
3ST Pharm Co. Ltd., Seoul, South Korea
Minjeong Kim and Michaela Jeong contributed equally to this study.
Correspondence: Hyukjin Lee
Abstract
mRNA-based protein replacement therapy has received much attention as a novel intervention in clinical disease treatment. Lipid nanoparticles (LNPs) are widely used for their therapeutic potential to efficiently deliver mRNA. However, clinical translation has been hampered by the immunogenicity of LNPs that may aggravate underlying disease states. Here, we report a novel ionizable LNP with enhanced potency and safety. The piperazine-based biodegradable ionizable lipid (244cis) was developed for LNP formulation and its level of protein expression and immunogenicity in the target tissue was evaluated. It was found that 244cis LNP enabled substantial expression of the target protein (human erythropoietin), while it minimally induced the secretion of monocyte chemoattractant protein 1 (MCP-1) as compared to other conventional LNPs. Selective lung targeting of 244cis LNP was further investigated in tdTomato transgenic mice with bleomycin-induced pulmonary fibrosis (PF). The repeated administration of 244cis LNP with Cre recombinase mRNA achieved complete transfection of lung endothelial cells (~80%) and over 40% transfection of Sca-1-positive fibroblasts. It was shown that 244cis LNP allows the repeated dose of mRNA without the loss of activity due to its low immunogenicity. Our results demonstrate that 244cis LNP has great potential for the treatment of chronic diseases in the lungs with improved potency and safety.
논문정보
- Research article
- 2023년 05월 (BRIC 등록일 2023-05-30)
- 국내 연구진
- 의약학 > 약학
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