The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein(CRISPR/Cas)system was discovered in bacteria and archaea as an adaptive immunity system to protect against exogenous DNA(...The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein(CRISPR/Cas)system was discovered in bacteria and archaea as an adaptive immunity system to protect against exogenous DNA(Barrangou et al.,2007).This system has been developed into a powerful gene editing tool for eukaryotic genome manipulation that has therapeutic opportunities against hereditary diseases(Cong et al.,2013),especially monogenic diseases.展开更多
APOBECs（apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like） are a family of cytidine deaminases that prefer single-stranded nucleic acids as substrates. Besides their physiological functions,APOBEC fam...APOBECs（apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like） are a family of cytidine deaminases that prefer single-stranded nucleic acids as substrates. Besides their physiological functions,APOBEC family members have been found to cause hypermutations of cancer genomes, which could be correlated with cancer development and poor prognosis. Recently, APOBEC family members have been combined with the versatile CRISPR/Cas9 system to perform targeted base editing or induce hypermutagenesis. This combination improved the CRISPR/Cas9-mediated gene editing at single-base precision, greatly enhancing its usefulness. Here, we review the physiological functions and structural characteristics of APOBEC family members and their roles as endogenous mutators that contribute to hypermutations during carcinogenesis. We also review the various iterations of the APOBEC-CRISPR/Cas9 gene-editing tools, pointing out their features and limitations as well as the possibilities for future developments.展开更多
基金surported by Research Foundation of Shanghai General Hospital。
文摘The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein(CRISPR/Cas)system was discovered in bacteria and archaea as an adaptive immunity system to protect against exogenous DNA(Barrangou et al.,2007).This system has been developed into a powerful gene editing tool for eukaryotic genome manipulation that has therapeutic opportunities against hereditary diseases(Cong et al.,2013),especially monogenic diseases.
基金supported by grants from the National Natural Science Foundation of China (Nos. 31600619 and 31600654)Shanghai Municipal Science and Technology Commission (Nos. 16PJ1407000 and 16PJ1407500)
文摘APOBECs（apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like） are a family of cytidine deaminases that prefer single-stranded nucleic acids as substrates. Besides their physiological functions,APOBEC family members have been found to cause hypermutations of cancer genomes, which could be correlated with cancer development and poor prognosis. Recently, APOBEC family members have been combined with the versatile CRISPR/Cas9 system to perform targeted base editing or induce hypermutagenesis. This combination improved the CRISPR/Cas9-mediated gene editing at single-base precision, greatly enhancing its usefulness. Here, we review the physiological functions and structural characteristics of APOBEC family members and their roles as endogenous mutators that contribute to hypermutations during carcinogenesis. We also review the various iterations of the APOBEC-CRISPR/Cas9 gene-editing tools, pointing out their features and limitations as well as the possibilities for future developments.
