P۵۳-inactivating mutations introduces a path efficientCRISPR–Cas۹ genome editing

سال انتشار: 1400
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 132

نسخه کامل این مقاله ارائه نشده است و در دسترس نمی باشد

استخراج به نرم افزارهای پژوهشی:

لینک ثابت به این مقاله:

شناسه ملی سند علمی:

CHGGE01_089

تاریخ نمایه سازی: 22 شهریور 1401

چکیده مقاله:

CRISPR–Cas۹-mediated genome editing is increasingly widespread inbiological research, and it might have therapeutic implications .In addition,CRISPR/Cas۹ has changed the way we alter genomes and do genome-widescreening in human cells. This editing method often facilitates themodification of the genome by introducing Double Strand Breaks (DSBs) attargeted sites. Introduction of DSB mediated by the programmed-nucleasestriggers the activation of either non-homologous end joining (NHEJ) or byhomology-directed repair (HDR), recruiting the components of the repairsystem to the targeted site, restoring the wild-type genotype or requisitiondesired changes. On the contrary, DSBs can cause unwanted genomicmodifications such as translocations, as well as the activation of p۵۳responses in cells. In response to DNA-damaging stimuli, the tumorsuppressor p۵۳ triggers cell cycle arrest, cellular senescence, and/orapoptosis, preserving genome stability. As a result, it's not unexpected thatthe p۵۳ pathway is activated in response to CRISPR/Cas۹ editing, and theinduction of its target gene, p۲۱. Therefore the activation of p۵۳ responsesin cells may decrease the number of transformed cells and their viability.However, inhibiting p۵۳ makes the cell vulnerable to chromosomalrearrangements and other tumor-causing mutations. To improve the balance,the temporary p۵۳ genetic inactivation may prevent the damage responseand increase the efficacy of precision genome editing in the endogenousHDR pathway. Future research should focus on understanding the Cas۹-induced DNA damage response in order to improve the efficacy of genomeediting.

کلیدواژه ها:

نویسندگان

Maryam Ranjbar

Department of Medical Genetics, Shiraz University of Medical Sciences, Shiraz, Iran

Marjan Nourigorji

Department of Medical Genetics, Shiraz University of Medical Sciences, Shiraz, Iran

Farzaneh Vahedi

Shiraz University of Medical Sciences,Department of Medical Biotechnology