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Locked Nucleic Acid AntimiR Therapy for the Heart

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Cardiac Gene Therapy

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2573))

Abstract

Coronary heart disease is one of the leading causes of death in industrialized nations. Even though revascularization strategies improved the outcome of patients after acute myocardial infarction, about 30% of patients develop chronic heart failure. Ischemic heart disease and heart failure are characterized by an adverse remodeling of the heart, featuring cardiomyocyte hypertrophy, increased fibrosis, and capillary rarefaction. Therefore, novel therapeutic approaches for the treatment of heart failure, such as reducing ischemia/reperfusion injury, fibrosis, or hypertrophy, are needed. Here microRNAs (miRNAs) come into play. For heart failure, cardiac stress and several cardiovascular diseases, individual miRNAs, and whole miRNA clusters have been implicated as disease relevant and dysregulated. miRNAs are short non-coding RNA molecules of about 22 nucleotides, and their inhibitors are 8–15 nucleotides long plus a sugar-ring (LNA, locked nucleid acid) or cholesterol ending (AntagomiR). Modulation of miRNAs might serve as therapeutic targets through miRNA knockdown or overexpression via miRNA mimics. Due to their pleiotropic mode of action and the presence of individual miRNAs in a variety of tissues and cells, a local, target region-oriented application is important to achieve therapeutic effects and at the same time reducing adverse effects in other off-target organs and tissues. Due to their small size, the miRNA inhibitors are able to pass endothelial barrier at both arterial and venous sides of the bloodstream vessels. For these reasons, the gold standard administration route of miRNA modulators for therapeutic approaches of the left ventricle is the anterograde application into one or both coronary arteries via an over-the-wire (OTW) balloon. In this chapter we provide a comprehensive description of the anterograde application procedure in a large animal model such as pig. Of a particular note, this methodology is a standard procedure in catheter laboratories, a key characteristic that allows therapeutic translation from large animals to patients.

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Authors and Affiliations

  1. Deutsches Primatenzentrum GmbH, Göttingen, Germany

    Sabine Samolovac & Rabea Hinkel

Authors
  1. Sabine Samolovac
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  2. Rabea Hinkel
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Correspondence to Rabea Hinkel .

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Editors and Affiliations

  1. Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Kiyotake Ishikawa

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Samolovac, S., Hinkel, R. (2022). Locked Nucleic Acid AntimiR Therapy for the Heart. In: Ishikawa, K. (eds) Cardiac Gene Therapy. Methods in Molecular Biology, vol 2573. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2707-5_12

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  • DOI: https://doi.org/10.1007/978-1-0716-2707-5_12

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2706-8

  • Online ISBN: 978-1-0716-2707-5

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