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Therapeutic Editing of the TP53 Gene: Is CRISPR/Cas9 an Option?

1
Kazan Federal University, 420008 Kazan, Russia
2
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia
*
Author to whom correspondence should be addressed.
Genes 2020, 11(6), 704; https://doi.org/10.3390/genes11060704
Received: 6 May 2020 / Revised: 21 June 2020 / Accepted: 23 June 2020 / Published: 25 June 2020
(This article belongs to the Special Issue CRISPR-Cas: Interactions with Genome and Physiological Maintenance)
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. View Full-Text
Keywords: TP53; mutation; CRISPR/Cas9 gene editing; base editing; prime editing; epigenome regulation; clinical trial TP53; mutation; CRISPR/Cas9 gene editing; base editing; prime editing; epigenome regulation; clinical trial
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Mirgayazova, R.; Khadiullina, R.; Chasov, V.; Mingaleeva, R.; Miftakhova, R.; Rizvanov, A.; Bulatov, E. Therapeutic Editing of the TP53 Gene: Is CRISPR/Cas9 an Option? Genes 2020, 11, 704.

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