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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Delivery of Modified mRNA in a Myocardial Infarction Mouse Model
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A Systemic Selective Modified mRNA Delivery Platform for Preventing Chemotherapy-Induced Cardiotoxicity.

Jimeen Yoo1,2,3, Gayatri Mainkar1,2,3, Matteo Ghiringhelli1,2,3

  • 1Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|January 16, 2026
PubMed
Summary
This summary is machine-generated.

This study introduces a novel mRNA therapy platform (cmSMRTs) for minimally invasive, targeted delivery to the heart. It effectively prevents chemotherapy-induced cardiotoxicity without compromising anti-tumor efficacy.

Keywords:
Dox cardiotoxicitycardiac‐selective deliverymodified mRNA

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Area of Science:

  • Cardiology
  • Oncology
  • Biotechnology

Background:

  • Doxorubicin (Dox) chemotherapy causes dose-dependent cardiotoxicity, limiting its clinical use.
  • Doxorubicin-induced cardiotoxicity involves oxidative stress and ceramide accumulation in cardiomyocytes.
  • Current mRNA therapies require invasive delivery, hindering widespread application.

Purpose of the Study:

  • To develop a minimally invasive, cardiac-selective mRNA delivery system for preventing Doxorubicin-induced cardiotoxicity.
  • To evaluate the efficacy of acid ceramidase (AC) modified mRNA (modRNA) delivered via a novel platform in preclinical models.

Main Methods:

  • Developed a cardiac-selective mRNA translational system (cmSMRTs) using lipid nanoparticles for intravenous delivery.
  • Utilized microRNA-guided translational control (miR143 and miR122) for enhanced cardiac targeting and reduced off-target expression.
  • Assessed AC modRNA efficacy in vitro using Doxorubicin-treated human induced pluripotent stem cell-derived cardiomyocytes.
  • Evaluated cmSMRTs 143-122 in chronic Doxorubicin-induced cardiotoxicity mouse models.

Main Results:

  • In vitro, AC treatment preserved cardiomyocyte structure, calcium handling, and mitochondrial function.
  • Intravenous delivery of AC modRNA via cmSMRTs prevented cardiac dysfunction, fibrosis, and atrophy in Doxorubicin-treated mice.
  • The therapy demonstrated cardiac selectivity, with no compromise to Doxorubicin's anti-tumor efficacy or overall toxicity.

Conclusions:

  • cmSMRTs 143-122 represents a promising, minimally invasive mRNA therapy platform for preventing chemotherapy-induced cardiotoxicity.
  • This approach offers a potential strategy to improve the safety and tolerability of Doxorubicin treatment.
  • The study highlights the potential of targeted mRNA delivery for managing treatment-related toxicities in cancer patients.