Nuclear and mitochondrial DNA editing in human cells with zinc finger deaminases

التفاصيل البيبلوغرافية
العنوان:	Nuclear and mitochondrial DNA editing in human cells with zinc finger deaminases
المؤلفون:	Lim, Kayeong, Cho, Sung-Ik, Kim, Jin-Soo
المساهمون:	Institute for Basic Science
المصدر:	Nature Communications ; volume 13, issue 1 ; ISSN 2041-1723
بيانات النشر:	Springer Science and Business Media LLC
سنة النشر:	2022
الوصف:	Base editing in nuclear DNA and mitochondrial DNA (mtDNA) is broadly useful for biomedical research, medicine, and biotechnology. Here, we present a base editing platform, termed zinc finger deaminases (ZFDs), composed of custom-designed zinc-finger DNA-binding proteins, the split interbacterial toxin deaminase DddA tox , and a uracil glycosylase inhibitor (UGI), which catalyze targeted C-to-T base conversions without inducing unwanted small insertions and deletions (indels) in human cells. We assemble plasmids encoding ZFDs using publicly available zinc finger resources to achieve base editing at frequencies of up to 60% in nuclear DNA and 30% in mtDNA. Because ZFDs, unlike CRISPR-derived base editors, do not cleave DNA to yield single- or double-strand breaks, no unwanted indels caused by error-prone non-homologous end joining are produced at target sites. Furthermore, recombinant ZFD proteins, expressed in and purified from E. coli , penetrate cultured human cells spontaneously to induce targeted base conversions, demonstrating the proof-of-principle of gene-free gene therapy.
نوع الوثيقة:	article in journal/newspaper
اللغة:	English
DOI:	10.1038/s41467-022-27962-0
الاتاحة:	http://dx.doi.org/10.1038/s41467-022-27962-0 https://www.nature.com/articles/s41467-022-27962-0.pdf https://www.nature.com/articles/s41467-022-27962-0
Rights:	https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0
رقم الانضمام:	edsbas.3892BEC0
قاعدة البيانات:	BASE

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الوصف
DOI:	10.1038/s41467-022-27962-0