Genome Editing in Cardiovascular Biology
Genome editing has emerged as a powerful tool in research and is entering the stage of therapeutic applications. In the cardiovascular field, its role in basic and translational research is well established. However, biological and technical barriers currently hamper the therapeutic potential of genome editing for cardiovascular diseases. This viewpoint discusses possible routes for promoting therapeutic use of genome editing in the cardiovascular system.
Genome editing has rapidly emerged as a powerful tool in basic and translational research. Zinc finger nucleases and TALENs (transcription activator-like effector nucleases) catalyzed the field initially. With the development of the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) system, the field is expanding even more rapidly because of its efficacy, specificity, and ease of use (Figure [A]). Generally, genome editing tools induce site-specific DNA double-strand breaks at a specific genomic site, resulting in the activation of the nonhomologous end-joining (NHEJ) and homologous recombination (HR) cellular endogenous double-strand break repair machinery (Figure [B]). Recent advances of the CRISPR technology also allow for RNA recognition, making it possible to cleave RNA, enhance or inhibit translation, support isolation of specific RNA:protein complexes, or induce specific post-transcriptional modifications.1 Genome editing tools can also be used to control gene expression on the transcriptional level. Deactivation of the catalytic site of CRISPR/Cas9 (dCas9) results in specific binding to the DNA without inducing double-strand breaks. Fusion of dCas9 to DNA-binding domains, such as activator or repressor domains, results in transcriptional activation or inhibition of a specific gene, respectively.2 Despite the major impact genome editing already has on basic and translational research, regulatory processes have delayed therapeutic applications from reaching the clinic. Nevertheless, effective new therapies are anticipated in the near future for various disease conditions, especially if major issues around safety and toxicity are resolved.