Endonucleases have been engineered to become powerful DNA editing tools such as ZFN, TALEN, the sturdy CRISPR–Cas system and the controversial NgAgo technology. However, these techniques are targeted to achieve targeted cleavage and are limited by sequence preferences.

The research team at Nanjing University published a breakthrough in Genome Biology on September 15. They developed a structure-guided new DNA editing technique that is no longer limited by target sequences. The author of this article is Guohua Zhou, a researcher at Jinling Hospital affiliated to Nanjing University School of Medicine, and Professor Qingshun Zhao and Minsheng Zhu at the Institute of Model Animals, Nanjing University.

FEN1 (flap endonuclease-1) is an endonuclease that recognizes the 3' flap structure. The researchers combined FEN1 with the Fn1 (Fok I) cleavage domain to create a structure-directed DNA editing tool, SGN. SGN (structure-guided endonuclease) recognizes the 3' flap structure formed by the target sequence and the guide DNA (gDNA), and cleaves the target sequence by Fn1 dimerization. Studies have shown that a pair of gDNA can direct SGN to correctly cleave reporter and endogenous genes in the genome of zebrafish embryos. The study indicated that SGN specifically recognizes and captures targets and accurately cleaves any DNA sequence.

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