Scholarlink

<p>Self-amplifying mRNA (saRNA) vectors hold promise for the sustained expression of mRNA vaccines in vivo. However, their inherently high immunogenicity and low-fidelity replication—stemming from the RNA viral genome’s replication mechanisms—limit their efficacy as replacements or adjuncts to protein therapies. Here we report an engineered viral protein genome-linked (VPg) saRNA vector derived from a Norovirus replicon, designed for rapid loading of therapeutic protein mRNAs in vitro. The engineered VPg saRNA is adapted for a range of therapeutic scenarios, including treatment of tumor-associated cachexia under conditions of translational restriction in cap-dependent metabolism, precise encoding of oncolytic mRNAs in vivo to achieve complex functionality, and therapy for graft-versus-host disease in highly auto-immune environments. VPg saRNA addresses key limitations of linear mRNA and conventional saRNA therapies, broadening the potential applications of mRNA-based treatments.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Engineered VPg saRNA achieves cap-independent, low-immunogenic and precise encoding of therapeutic proteins in vivo

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月27日

查看全文
  • Zunyong Feng,
  • Liuxi Chu,
  • Qiang Li,
  • Jing Zhou,
  • Ping Wu,
  • Xuanbo Zhang,
  • Yuanbo Pan,
  • Jianhua Zou,
  • Qun Chen,
  • Zhiliang Xu,
  • Liang Yan,
  • Yanjiao Huang,
  • Xiaokun Li,
  • Zhouguang Wang,
  • Xiaoyuan Chen

摘要

Self-amplifying mRNA (saRNA) vectors hold promise for the sustained expression of mRNA vaccines in vivo. However, their inherently high immunogenicity and low-fidelity replication—stemming from the RNA viral genome’s replication mechanisms—limit their efficacy as replacements or adjuncts to protein therapies. Here we report an engineered viral protein genome-linked (VPg) saRNA vector derived from a Norovirus replicon, designed for rapid loading of therapeutic protein mRNAs in vitro. The engineered VPg saRNA is adapted for a range of therapeutic scenarios, including treatment of tumor-associated cachexia under conditions of translational restriction in cap-dependent metabolism, precise encoding of oncolytic mRNAs in vivo to achieve complex functionality, and therapy for graft-versus-host disease in highly auto-immune environments. VPg saRNA addresses key limitations of linear mRNA and conventional saRNA therapies, broadening the potential applications of mRNA-based treatments.