Scholarlink

<p>Gene transfection via lipid nanoparticle (LNP)−mRNA complexes have tremendous potential for treating cardiac diseases. However, the transfection efficiency is poor and there is a lack of in vitro screening systems that predict transfection efficacy. Here we demonstrate a method for identifying LNP−mRNA complexes that diffuse efficiently within 3D cardiac micromuscles and transfect cardiomyocytes with high efficiency, using a phenotypic cardiac microphysiological system (MPS) constructed from a human induced pluripotent stem cell cardiomyocytes Cre-reporter line. LNP formulations containing an acid-degradable PEG–lipid had enhanced diffusion and gene editing efficiency in the cardiac MPS. The in vivo delivery of LNP−mRNA complexes, including luciferase and CRE mRNA, into Ai6 mice confirmed the cardiac MPS screening outcomes. Acid-degradable PEG-LNPs achieved notably superior transfection in the heart with reduced off-target liver uptake compared with standard LNP formulations. The cardiac MPS showed strong LNP transfection in vitro and pinpointed a promising formulation for in vivo mRNA delivery to the heart.</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

A microphysiological system for screening lipid nanoparticle−mRNA complexes predicts in vivo heart transfection efficacy

  • 期刊论文

  • 发表日期：

    2025年11月3日

查看全文
  • Gabriel Neiman,
  • Mauro W. Costa,
  • Hesong Han,
  • Sheng Zhao,
  • Tammy K. Ng,
  • Brian Siemons,
  • Tomohiro Nishino,
  • Yu Huang,
  • Shyam Lal,
  • Kenneth Wu,
  • Luke M. Judge,
  • Bruce R. Conklin,
  • Deepak Srivastava,
  • Niren Murthy,
  • Kevin E. Healy

摘要

Gene transfection via lipid nanoparticle (LNP)−mRNA complexes have tremendous potential for treating cardiac diseases. However, the transfection efficiency is poor and there is a lack of in vitro screening systems that predict transfection efficacy. Here we demonstrate a method for identifying LNP−mRNA complexes that diffuse efficiently within 3D cardiac micromuscles and transfect cardiomyocytes with high efficiency, using a phenotypic cardiac microphysiological system (MPS) constructed from a human induced pluripotent stem cell cardiomyocytes Cre-reporter line. LNP formulations containing an acid-degradable PEG–lipid had enhanced diffusion and gene editing efficiency in the cardiac MPS. The in vivo delivery of LNP−mRNA complexes, including luciferase and CRE mRNA, into Ai6 mice confirmed the cardiac MPS screening outcomes. Acid-degradable PEG-LNPs achieved notably superior transfection in the heart with reduced off-target liver uptake compared with standard LNP formulations. The cardiac MPS showed strong LNP transfection in vitro and pinpointed a promising formulation for in vivo mRNA delivery to the heart.