mRNA-Based Protein Replacement Therapy for the Heart

Ajit Magadum, Keerat Kaur, Lior Zangi

Research output: Contribution to journalReview articlepeer-review

57 Scopus citations

Abstract

Myocardial infarction (MI) and heart failure (HF) are the leading causes of death in the United States and in most other industrialized nations. MI leads to a massive loss of cardiomyocytes (CMs), which are replaced with non-CM cells, leading to scarring and, in most cases, HF. The adult mammalian heart has a low intrinsic regenerative capacity, mainly because of cell-cycle arrest in CMs. No effective treatment promoting heart regeneration is currently available. Recent efforts to use DNA-based or viral gene therapy approaches to induce cardiac regeneration post-MI or in HF conditions have encountered major challenges, mostly because of the poor and uncontrolled delivery of the introduced genes. Modified mRNA (modRNA) is a safe, non-immunogenic, efficient, transient, local, and controlled nucleic acid delivery system that can overcome the obstacles to DNA-based or viral approaches for cardiac gene delivery. We here review the use of modRNA in cardiac therapy, to induce cardioprotection and vascular or cardiac regeneration after MI. We discuss the current challenges in modRNA-based cardiac treatment, which will need to be overcome for the application of such treatment to ischemic heart disease. Modified mRNA (modRNA) is a new technology in the field of somatic gene transfer in the heart. modRNA can be used to improve the condition of ischemic injury by inducing cardiac and cardiovascular regeneration and cardiac proliferation. In this issue of Molecular The.rapy, Magadum et al. review the use of modRNA-based protein replacement therapy for the heart.

Original languageEnglish
Pages (from-to)785-793
Number of pages9
JournalMolecular Therapy
Volume27
Issue number4
DOIs
StatePublished - 10 Apr 2019

Keywords

  • cardiac regeneration
  • gene therapy
  • mRNA therapy

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