Application of CRISPR-Cas9 gene editing for congenital heart disease

Abstract

Clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR-Cas9) is an ancient prokaryotic defense system that precisely cuts foreign genomic DNA under the control of a small number of guide RNAs. The CRISPR-Cas9 system facilitates efficient double-stranded DNA cleavage that has been recently adopted for genome editing to create or correct inherited genetic mutations causing disease. Congenital heart disease (CHD) is generally caused by genetic mutations such as base substitutions, deletions, and insertions, which result in diverse developmental defects and remains a leading cause of birth defects. Pediatric CHD patients exhibit a spectrum of cardiac abnormalities such as septal defects, valvular defects, and abnormal chamber development. CHD onset occurs during the prenatal period and often results in early lethality during childhood. Because CRISPR-Cas9-based genome editing technology has gained considerable attention for its potential to prevent and treat diseases, we will review the CRISPR-Cas9 system as a genome editing tool and focus on its therapeutic application for CHD.

Diversity, Equity, And Inclusion (Dei) Quotient in The Age of Crispr-Cas 9: A Speculative Spectrum of Argumentation

“…It is not questionable if people with incurable ailments should undergo editorial intervention in their genetic code to enjoy good health. The spirit of the international consensus and ethical guidelines on applying CRISPR-Cas9 does not conflict with the preference of people with congenital ailments (Seok et al, 2021). In a way, they have a right to enjoy all the affordances of CRISPR-Cas9.…”

Chronic Heart Failure in Children: State of the Art and New Perspectives

“…In the genome editing field, CRISPR-Cas9 is a revolutionary system that permits the modification of specific sequences by insertion, deletion, or substitution using rationally designed templates. This technology has been tested using CHD animal models and has shown some promising results [ 56 ].…”

Insights into the Mechanism of CRISPR/Cas9-Based Genome Editing from Molecular Dynamics Simulations

“…Class I systems involve multiple Cas proteins, whereas class II systems involve only one protein for the interference step. − CRISPR/Cas systems are also divided into different types on the basis of the presence of unique genes (Cas3, Cas9, Cas10, Csf2, Cpf1, and Cas13 for Types I–VI, respectively). − A simple overview of the Cas protein components characteristic of each type has been depicted in Figure . The further classification into subtypes is more complicated, which takes into account several factors such as the presence of unique genes, evolutionary conservation of effector modules, and many more. , Involvement of a single Cas protein in the interference step has made the Class II system very attractive as a genome-editing tool, particularly the CRISPR/Cas9 system, which has extensively been used in numerous genome-editing applications. − CRISPR systems mostly target foreign DNA except for the type VI CRISPR/Cas13 system, which targets RNA …”

“…Clinical trials for the first in vivo application of Cas9 began in 2019 . Presently, CRISPR/Cas9 is used in vast applications in genome editing ranging from therapeutic applications − to plant − and fungal , biotechnology.…”