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Updated: Jul 31, 2025

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Optimization of Strategy for Modified mRNA Inducing Cardiac-Specific Expression in Mice.

Chenxing Huang1, Jianguo Jia1, Kejia Jin1

  • 1Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.

Journal of Cardiovascular Translational Research
|May 8, 2023
PubMed
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This summary is machine-generated.

Naked modified RNA (modRNA) delivered directly to the heart shows high cardiac expression. Lipid nanoparticle (LNP) delivery of modRNA enhances cardiac expression but also liver accumulation, which can be mitigated by liver-silencing modRNA.

Area of Science:

  • Biotechnology
  • Molecular Biology
  • Cardiovascular Research

Background:

  • Lipid nanoparticle (LNP)-modified RNA (modRNA) enhances modRNA stability but often leads to liver accumulation.
  • Optimizing modRNA delivery for targeted cardiac expression is crucial for therapeutic applications.
  • Current strategies require refinement to balance cardiac efficacy and minimize off-target organ accumulation.

Purpose of the Study:

  • To optimize strategies for enhancing cardiac expression efficiency of modRNA.
  • To evaluate the biodistribution and cardiac specificity of modRNA delivered via different methods.
  • To develop a liver-silencing modRNA to improve cardiac targeting.

Main Methods:

  • Synthesis of Luciferase (Luc)-modRNA and a liver-silencing variant (122Luc modRNA).
Keywords:
HeartIntramyocardial injectionLuciferasemodRNA

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  • Administration of naked modRNA and modRNA-LNP formulations via intramyocardial injection.
  • Bioluminescence imaging to quantify modRNA expression in the heart and liver.

    • Main Results:

    • Intramyocardial injection of naked Luc modRNA resulted in high cardiac but low liver expression.
    • Luc modRNA-LNP significantly increased cardiac (5-fold) and liver (15,000-fold) expression compared to naked modRNA.
    • 122Luc-modRNA-LNP reduced liver signal to 0.17% with only a slight drop in cardiac signal.

    Conclusions:

    • Intramyocardial injection of naked modRNA achieves effective cardiac-specific expression.
    • Liver-silencing modRNA (122modRNA-LNP) enhances cardiac expression specificity by reducing liver accumulation.
    • This strategy offers a promising approach for targeted cardiac gene delivery using modRNA-LNP.