Recent Advances in CRISPR/Cas9-Based Genome Editing Tools for Cardiac Diseases

Schreurs, Juliët; Sacchetto, Claudia; Colpaert, Robin M.W.; Vitiello, Libero; Calore, Martina

doi:10.3390/ijms222010985

Cited by 9 publications

(14 citation statements)

References 85 publications

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“…Furthermore, more characterization and optimization are needed in order to its therapeutic application. 45 Beyond that, despite the suggestive application of CRISPR technology including; genome editing, endogenous genes expression, epigenome editing, and edition of RNA, several challenges should be targeted in future studies.…”

Section: Discussionmentioning

confidence: 99%

A glance at the application of CRISPR/Cas9 gene-editing technology in cardiovascular diseases

Roshanravan

Tutunchi

Najafipour

et al. 2022

J Cardiovasc Thorac Res

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Cardiovascular diseases (CVDs) remain major causes of global mortality in the world. Genetic approaches have succeeded in discovery of the molecular basis of an increasing number of cardiac diseases. Genome editing strategies are one of the most effective methods for assisting therapeutic approaches. Potential therapeutic methods of correcting disease-causing mutations or of knocking out specific genes as approaches for the prevention of CVDs have gained substantial attention using genome editing techniques. Recently, the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system has become the most widely used genome-editing technology in molecular biology due to its benefits such as simple design, high efficiency, good repeatability, short-cycle, and costeffectiveness. In the present review, we discuss on the possibilities of applying the CRISPR/Cas9 genome editing tool in the CVDs.

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Section: Discussionmentioning

confidence: 99%

A glance at the application of CRISPR/Cas9 gene-editing technology in cardiovascular diseases

Roshanravan

Tutunchi

Najafipour

et al. 2022

J Cardiovasc Thorac Res

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“…However, the advent of CRISPR technology has allowed for in vivo or ex vivo therapeutic gene editing, depending on the tissue of interest [ 3 ]. For blood disorders such as β-thalassemia and sickle cell disease, infusion of ex vivo edited patient-derived hematopoietic stem cells has shown promise in treating those diseases [ 74 ]. Conversely, efficient and safe delivery systems are required for genome editing in cardiomyopathies.…”

Section: Reviewmentioning

confidence: 99%

“…Conversely, efficient and safe delivery systems are required for genome editing in cardiomyopathies. AAV has emerged as a leading candidate for delivering CRISPR/Cas9 components to the heart [ 74 ]. However, the limited packaging capacity of AAV (≈4.7 kb) necessitates separate vectors for the most commonly used Cas9 from Streptococcus pyogenes and its single-guide RNA [ 74 ].…”

Section: Reviewmentioning

confidence: 99%

“…AAV has emerged as a leading candidate for delivering CRISPR/Cas9 components to the heart [ 74 ]. However, the limited packaging capacity of AAV (≈4.7 kb) necessitates separate vectors for the most commonly used Cas9 from Streptococcus pyogenes and its single-guide RNA [ 74 ]. To address this issue, several small Cas9 orthologs have been engineered [ 74 ].…”

Section: Reviewmentioning

confidence: 99%

“…However, the limited packaging capacity of AAV (≈4.7 kb) necessitates separate vectors for the most commonly used Cas9 from Streptococcus pyogenes and its single-guide RNA [ 74 ]. To address this issue, several small Cas9 orthologs have been engineered [ 74 ]. The delivery of base editors (BEs) or prime editors (PEs) is also limited by AAV packaging capacity, although a dual-AAV system utilizing trans-splicing inteins has been shown to reconstitute full-length BEs and PEs [ 74 ].…”

Section: Reviewmentioning

confidence: 99%

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Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) in Cardiovascular Disease: A Comprehensive Clinical Review on Dilated Cardiomyopathy

Ganipineni¹,

Gutlapalli²,

Danda³

et al. 2023

Cureus

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Dilated cardiomyopathy (DCM) is one of the most important causes of heart failure in developed and developing countries. Currently, most medical interventions in the treatment of DCM are mainly focused on mitigating the progression of the disease and controlling the symptoms. The vast majority of patients who survive till the late stages of the disease require cardiac transplantation; this is exactly why we need novel therapeutic interventions and hopefully treatments that can reverse the clinical cardiac deterioration in patients with DCM. Clustered regularly interspaced short palindromic repeats (CRISPR) technology is a novel therapeutic intervention with such capacity; it can help us edit the genome of patients with genetic etiology for DCM and potentially cure them permanently. This review provides an overview of studies investigating CRISPR-based gene editing in DCM, including the use of CRISPR in DCM disease models, phenotypic screening, and genotype-specific precision therapies. The review discusses the outcomes of these studies and highlights the potential benefits of CRISPR in developing novel genotype-agnostic therapeutic strategies for the genetic causes of DCM. The databases we used to extract relevant literature include PubMed, Google Scholar, and Cochrane Central. We used the Medical Subject Heading (MeSH) strategy for our literature search in PubMed and relevant search keywords for other databases. We screened all the relevant articles from inception till February 22, 2023. We retained 74 research articles after carefully reviewing each of them. We concluded that CRISPR gene editing has shown promise in developing precise and genotype-specific therapeutic strategies for DCM, but there are challenges and limitations, such as delivering CRISPR-Cas9 to human cardiomyocytes and the potential for unintended gene targeting. This study represents a turning point in our understanding of the mechanisms underlying DCM and paves the way for further investigation into the application of genomic editing for identifying novel therapeutic targets. This study can also act as a potential framework for novel therapeutic interventions in other genetic cardiovascular diseases.

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CRISPR/Cas9 correction of a dominant cis-double-variant in COL1A1 isolated from a patient with osteogenesis imperfecta increases the osteogenic capacity of induced pluripotent stem cells

Cao

Ren

et al. 2020

Journal of Bone and Mineral Research

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Osteogenesis imperfecta (OI) is a hereditary skeletal disorder that is mainly caused by variants in COL1A1/2. So far, no specific treatment has been developed to correct its underlying etiology. We aimed to gain a better understanding of the pathological mechanisms of OI and develop gene therapies to correct OI-causing variants. A de novel cis-double-variant c.[175C>T; 187T>A] in COL1A1 was identified from a 5-year-old OI patient by whole-exome sequencing (WES). Three peptide nucleic acids (PNAs) were designed and then transfected patient-derived fibroblasts. PNA2 affected the translational strand and induced an optimal interfering effect at 0.25μM concentration, proved by Sanger sequencing, qPCR, Western blot, and immunostaining. Additionally, induced pluripotent stem cells (iPSCs) were cultured from patient-derived fibroblasts. Clones of iPSCs with c.187T>A variant and those with both variants largely restored their osteogenic capacities after CRISPR/Cas9 gene editing, which corrected the variants. Importantly, correcting c.187T>A variant alone in CRISPR-edited iPSCs was sufficient to alleviate OI phenotypes, as indicated by increased levels of COL1A1, COL1A2, ALP mRNAs, and COL1A1 protein. Our findings suggest that c.187T>A is the dominant variant of cis-double-variant in COL1A1 that led to OI, and PNA interference and CRISPR/Cas9 gene editing may be new therapeutic tools for OI treatment.

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Recent Advances in CRISPR/Cas9-Based Genome Editing Tools for Cardiac Diseases

Cited by 9 publications

References 85 publications

A glance at the application of CRISPR/Cas9 gene-editing technology in cardiovascular diseases

A glance at the application of CRISPR/Cas9 gene-editing technology in cardiovascular diseases

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) in Cardiovascular Disease: A Comprehensive Clinical Review on Dilated Cardiomyopathy

CRISPR/Cas9 correction of a dominant cis-double-variant in COL1A1 isolated from a patient with osteogenesis imperfecta increases the osteogenic capacity of induced pluripotent stem cells

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