封装于脂质纳米颗粒中的金纳米颗粒-mRNA缀合物用于多种mRNA的协同共递送
Gold Nanoparticle-mRNA Conjugates Encapsulated in Lipid Nanoparticles for Coordinated Codelivery of Multiple mRNAs.
作者信息
Hwang Dajeong, Park Sin A, Kim Jae Hoon, Lee Seung-Yeul, Lee Jaebeom, Kim Han Sang, Kim Kyung-A, Lee Seung-Hoon, Oh Tae Jeong, Lee Jaewook, An Sungwhan
机构信息
Genomictree Inc, 44-6 Techno 10-ro, Yuseong-gu, Daejeon 34027, Republic of Korea.
Department of Chemistry and Department of Chemical Engineering and Applied Chemistry, Chungnam National University, 99 Daehak-ro, Gung-dong, Yuseong-gu, Daejeon 34134, Republic of Korea.
出版信息
ACS Omega. 2025 Jul 25;10(30):32998-33007. doi: 10.1021/acsomega.5c02145. eCollection 2025 Aug 5.
Gold nanoparticles (AuNPs) can be engineered to be utilized as carriers via anchoring multiple nucleic acids, including mRNAs, in specific ratios. However, the negative charge of mRNA-AuNP conjugates presents significant challenges for efficient cellular uptake and subsequent expression. To overcome this limitation, we developed a delivery system that combines mRNA-AuNP conjugation with lipid nanoparticles (LNPs) to enhance intracellular delivery. In our approach, AuNPs were functionalized with a thiolated antisense leader sequence (ALS), oligonucleotides complementary to the 5'-end leader sequence of the 5'-untranslated region (UTR) of the mRNA. This functionalization resulted in the formation of mRNA-ALS-AuNP conjugates, which were then encapsulated within LNPs. When we compared the ALS-AuNP@LNP constructs to ALS-AuNPs alone, ALS-AuNP@LNP demonstrated superior delivery and expression of () mRNA across multiple cell lines, as evidenced by robust green fluorescence. Furthermore, this system enables the precise codelivery of multiple mRNAs in defined ratios, as demonstrated by the successful codelivery of and mRNAs. These findings highlight the potential of the mRNA-ALS-AuNP@LNP platform as an effective and versatile tool for advancing mRNA-based therapeutics and vaccine development.
金纳米颗粒(AuNPs)可以通过以特定比例锚定包括mRNA在内的多种核酸,设计用作载体。然而,mRNA-AuNP缀合物的负电荷对有效的细胞摄取和随后的表达提出了重大挑战。为了克服这一限制,我们开发了一种递送系统,该系统将mRNA-AuNP缀合与脂质纳米颗粒(LNPs)相结合,以增强细胞内递送。在我们的方法中,AuNPs用硫醇化反义前导序列(ALS)功能化,ALS是与mRNA的5'-非翻译区(UTR)的5'-末端前导序列互补的寡核苷酸。这种功能化导致形成mRNA-ALS-AuNP缀合物,然后将其封装在LNPs内。当我们将ALS-AuNP@LNP构建体与单独的ALS-AuNPs进行比较时,ALS-AuNP@LNP在多个细胞系中表现出优异的()mRNA递送和表达,强烈的绿色荧光证明了这一点。此外,该系统能够以确定的比例精确共递送多种mRNA,如和mRNA的成功共递送所示。这些发现突出了mRNA-ALS-AuNP@LNP平台作为推进基于mRNA的治疗和疫苗开发的有效且通用工具的潜力。
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