Im San Hae, Chung Youseung, Duskunovic Nevena, Choi Heewon, Park Su-Hyung, Chung Hyun Jung
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea.
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea.
Adv Healthc Mater. 2024 Dec;13(31):e2401868. doi: 10.1002/adhm.202401868. Epub 2024 Oct 3.
An effective delivery platform is crucial for the development of mRNA vaccines and therapeutics. Here, a versatile platform utilizing cholesterol-modified oligonucleotides (L-oligo) that bind to the mRNA within lipid nanoparticles (LNP), and enables the effective delivery of the mRNA into target cells is introduced. mRNA incorporated into LNPs via linkage with L-oligo, termed oligonucleotide-linked LNP (lnLNP), is superior in cellular uptake and transfection efficiency in target cells in vitro and in vivo, compared to the conventional LNP formulations. It is further applied lnLNP as an mRNA vaccine platform for SARS-CoV-2, demonstrating robust induction of neutralizing activity as well as polyfunctional SARS-CoV-2-specific T-cell response in vivo. The current strategy can be versatilely applied to different LNP platforms, for vaccine and therapeutic applications against various diseases, such as infections and cancers.
一个有效的递送平台对于mRNA疫苗和治疗药物的开发至关重要。在此，介绍了一种通用平台，该平台利用与脂质纳米颗粒（LNP）内的mRNA结合的胆固醇修饰寡核苷酸（L-oligo），并能够将mRNA有效递送至靶细胞。通过与L-oligo连接而掺入LNP的mRNA，称为寡核苷酸连接的LNP（lnLNP），与传统的LNP制剂相比，在体外和体内靶细胞的细胞摄取和转染效率方面更具优势。它进一步将lnLNP用作针对SARS-CoV-2的mRNA疫苗平台，在体内显示出强大的中和活性诱导以及多功能的SARS-CoV-2特异性T细胞反应。当前策略可广泛应用于不同的LNP平台，用于针对各种疾病（如感染和癌症）的疫苗和治疗应用。
