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

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Abstract

Lipid nanoparticle (LNP)-coated-modified RNA(modRNA) has been developed for enhancing the stability of modRNA, but it tends to accumulate in liver. The current study aimed to optimize strategy for increasing cardiac expression efficiency of modRNA. We synthesized Luciferase (Luc)-modRNA, and also developed 122Luc modRNA, a liver silencing Luc modRNA. Intramyocardial injection of naked Luc modRNA induced high bioluminescence signal in heart, but very low in other organs including liver. Luc modRNA-LNP injection showed the signal was increased by 5 folds in the heart and by 15,000 folds in the liver, compared to naked Luc modRNA group. In comparison with Luc modRNA-LNP group, the liver signal was decreased to 0.17%, while cardiac signal showed a slight drop by intramyocardial injection of 122Luc-modRNA-LNP. Our data revealed that intramyocardial injection of naked modRNA could effectively induced cardiac-specific expression. For cardiac delivery of Luc modRNA-LNP, 122modRNA-LNP enhances specificity of cardiac expression by abolishing liver signal.

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Data Availability

All data generated or analyzed during this study are included in this article. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We think Bingyu Li and Guoping Zhang for technical support for this study.

Funding

This study was support by the National Natural Science Foundation of China (82070232) and Program of Shanghai Academic Research leader (21XD1403300 for Hui Gong and 22XD1423300 for Yuxiang Dai).

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Author notes

  1. Chenxing Huang, Jianguo Jia, and Kejia Jin contributed equally to this work.

Authors and Affiliations

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

    Chenxing Huang, Jianguo Jia, Kejia Jin, Yan Zou, Jinzhong Lin, Yuxiang Dai & Hui Gong

  2. State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, China

    Shudan Tan & Jinzhong Lin

  3. Shanghai RNACure Biopharma Co., 200438, Ltd, Shanghai, China

    Jing Lu

  4. State Key Laboratory of Quality Research in Chinese Medicine and School of Pharmacy, Macau University of Science and Technology, Macau, 999078, China

    Yizhun Zhu

  5. Shanghai Medical College and Zhongshan Hospital Immunotherapy Translational Research Center, Shanghai, 200030, China

    Yuxiang Dai & Hui Gong

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  1. Chenxing Huang
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  2. Jianguo Jia
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  4. Yan Zou
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  8. Jinzhong Lin
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  9. Yuxiang Dai
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  10. Hui Gong
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Correspondence to Yuxiang Dai or Hui Gong.

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Ethics Approval

All animal experiments were followed and approved by the Institutional Animal Use and Care Committee of Zhongshan Hospital, Fudan University. No human studies were carried out by the authors for this article.

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The authors declare no competing interests.

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Associate Editor Guoping Li oversaw the review of this article.

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Huang, C., Jia, J., Jin, K. et al. Optimization of Strategy for Modified mRNA Inducing Cardiac-Specific Expression in Mice. J. of Cardiovasc. Trans. Res. 16, 1078–1084 (2023). https://doi.org/10.1007/s12265-023-10392-8

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  • DOI: https://doi.org/10.1007/s12265-023-10392-8

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