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Gene editing and therapy in acquired and inherited cardiovascular disorders

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Abstract

Gene editing and therapy holds immense promise in addressing cardiovascular disorders by enabling precise modifications to the genetic groundworks of these conditions. This technology offers a targeted approach to correct or mitigate not only the genetic mutations that are responsible for inherited cardiovascular diseases, such as hypertrophic cardiomyopathy or familial hypercholesterolemia (FH), but also in controlling and regulating the genes in conditions that are age-related or that arise due to unnecessary gene activity, which often lack effective treatments. By editing the relevant genes, we aim to reduce disease severity, improve heart function, prevent future episodes and potentially improve the health span. Recent trials involving gene therapy and gene editing in cardiovascular disorders have revolutionized treatment strategies, offering hope for patients with genetic predispositions to heart and vessel-related ailments and advancing the pursuit for more personalized and effective therapies. In this review, we have consolidated the genetic mutations causing cardiovascular diseases (CVDs) followed by latest advancements in the gene editing technologies and their therapeutic implications along with involved ethical challenges and risk factors.

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Abbreviations

AAV:

Adeno associated virus

CRISPR:

Clustered regularly interspaced short palindromic repeats

Cas:

CRISPR associated protein

CVDs:

Cardiovascular diseases

iPSC:

Induced pluripotent stem cells

FH:

Familial hypercholesterolemia

PAH:

Pulmonary arterial hypertension

FTAAD:

Familial thoracic aortic aneurysm and dissection

ZFNs:

Zinc-finger nucleases

PAM:

Protospacer adjacent motif

HCM:

Hypertrophic cardiomyopathy

sgRNA:

Single-guide RNA

crRNA:

CRISPR-RNAs

tracrRNA:

trans-activating CrRNA

TALENS:

Transcription activator–like effector nucleases

VSMCs:

Vascular smooth muscle cells

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  1. Sushmitha Duddu and Rituparna Chakrabarti have contributed equally to this work.

Authors and Affiliations

  1. School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal, India

    Sushmitha Duddu, Rituparna Chakrabarti, Pooja Sharma & Praphulla Chandra Shukla

  2. Department of Pathology, All India Institute of Medical Sciences, Gorakhpur, Uttar Pradesh, India

    Deepika Gupta

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  1. Sushmitha Duddu
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  2. Rituparna Chakrabarti
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  3. Pooja Sharma
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  4. Deepika Gupta
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  5. Praphulla Chandra Shukla
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DS, RC, PS, and DG—wrote the manuscript. PCS—ideation and finalization of the manuscript.

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Correspondence to Praphulla Chandra Shukla.

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Duddu, S., Chakrabarti, R., Sharma, P. et al. Gene editing and therapy in acquired and inherited cardiovascular disorders. Nucleus 67, 237–250 (2024). https://doi.org/10.1007/s13237-024-00480-8

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  • DOI: https://doi.org/10.1007/s13237-024-00480-8

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