Therapeutic Editing of the TP53 Gene: Is CRISPR/Cas9 an Option?
The TP53 gene encodes the transcription factor and oncosuppressor p53 protein that regulates a multitude of intracellular metabolic pathways involved in DNA damage repair, cell cycle arrest, apoptosis, and senescence. In many cases, alterations (e.g., mutations of the TP53 gene) negatively affect these pathways resulting in tumor development. Recent advances in genome manipulation technologies, CRISPR/Cas9, in particular, brought us closer to therapeutic gene editing for the treatment of cancer and hereditary diseases. Genome-editing therapies for blood disorders, blindness, and cancer are currently being evaluated in clinical trials. Eventually CRISPR/Cas9 technology is expected to target TP53 as the most mutated gene in all types of cancers. A majority of TP53 mutations are missense which brings immense opportunities for the CRISPR/Cas9 system that has been successfully used for correcting single nucleotides in various models, both in vitro and in vivo. In this review, we highlight the recent clinical applications of CRISPR/Cas9 technology for therapeutic genome editing and discuss its perspectives for editing TP53 and regulating transcription of p53 pathway genes.
['Mirgayazova|Regina|R|', 'Khadiullina|Raniya|R|', 'Chasov|Vitaly|V|', 'Mingaleeva|Rimma|R|', 'Miftakhova|Regina|R|', 'Rizvanov|Albert|A|0000-0002-9427-5739', 'Bulatov|Emil|E|0000-0003-2961-0032']
D064113:CRISPR-Cas Systems D004260:DNA Repair D000072669:Gene Editing D005786:Gene Expression Regulation D016678:Genome D006801:Humans D009154:Mutation D009369:Neoplasms D016159:Tumor Suppressor Protein p53
TP53 mutation clinical trial CRISPR/Cas9 gene editing base editing epigenome regulation prime editing