假尿苷修饰体外转录mRNA在翻译过程中发生的+1核糖体框架移码
Pseudouridine-modified in vitro-transcribed mRNA Caused+1 Ribosomal Frameshifting During Protein Translation
于永利1
作者信息
- 1. 吉林大学基础医学院免疫系,长春 130021
- 折叠
摘要
为应对世界范围内的COVID-19疫情,假尿苷(Ψ)修饰的体外转录mRNA(Ψ-IVT-mRNA)被授权应用于SARS-Cov-2 mRNA疫苗.最近,Ψ-IVT-mRNA被发现在翻译蛋白质时发生核糖体"滞顿",导致+1核糖体移码,在体外和体内翻译出异常的蛋白质.在接种SARS-Cov-2 mRNA疫苗的人群,这种异常蛋白可能激发脱靶T细胞反应或抗体反应或产生其它意想不到的副作用.这一发现对研制有效"安全"的mRNA疫苗/药物有"警示"和指导意义.
Abstract
Pseudouridine(Ψ)-modified in vitro-transcribed mRNA(Ψ-IVT-mRNA)is used in two li-censed SARS-CoV-2 mRNA vaccines in response to the COVID-19 pandemic worldwide.Recently the Ψ-IVT-mRNA has been demonstrated to cause ribosome stalling and lead to+1 ribosomal frameshifting both in vitro and in vivo,resulting in aberrant protein products.The aberrant proteins may have the potential to induce off-target T-cell or antibody responses and other unintended side effects in people vaccinated with SARS-CoV-2 mRNA vaccines.The finding highlights a key aspect of developing mRNA-based vaccines/therapeutics with improved outcomes.
关键词
SARS-CoV-2疫苗/体外转录mRNA/假尿苷修饰/核糖体框架移码Key words
SARS-CoV-2 vaccines/in vitro transcribed mRNA/pseudouracil modification/ribosomal frameshifting引用本文复制引用
出版年
2024
NETL
NSTL
万方数据