2022年8月5日 · The IscB protein has been shown to work as a programmable RNA-guided endonuclease that is functionally similar to Cas9 nuclease, while also requiring a target-adjacent motif (TAM, 5′-NWRRNA-3...

2024年8月15日 · As the evolutionary ancestor of Cas9 nuclease, IscB proteins serve as compact RNA-guided DNA endonucleases and nickases, making them strong candidates for base editing.

2022年11月7日 · Transposon-encoded IscB family proteins are RNA-guided nucleases in the OMEGA (obligate mobile element-guided activity) system, and likely ancestors of the RNA-guided nuclease Cas9 in the type...

IscB已经具备了很多spCas9的优点，比如有两个酶活性位点，分别负责一条DNA单链的切割；又比如ωRNA的结构较为复杂，便于进行改造。 而IscB最大的优势还是其非常小的体积，为递送提供了极大的便利，同时也就腾出了巨大的改造空间。 IscB在微生物中分别广泛，相信在不久的将来，应该能够筛选到在真核细胞中编辑效率和靶向特异性达到spCas9水平的IscB，进一步加速基因编辑科研和临床的发展。 参考文献. [1] EngineeredCRISPR-Cas9 nuclease with expanded targeting …

2022年5月26日 · The evolutionary origin of CRISPR-Cas9 has been traced to the transposon-encoded nuclease IscB. A fraction of the size of Cas9, IscB is just as active as Cas9 in RNA-guided DNA cleavage in test tubes. How did it gradually morph into Cas9? Can we take advantage of its miniature size for expanded genome-editing usage?

2022年11月7日，张锋、Hiroshi Nishimasu 等人在 Nature Communications 期刊发表了题为：Structure of the IscB–ωRNA ribonucleoprotein complex, the likely ancestor of CRISPR-Cas9 的研究论文【2】。 该研究 解析了IscB蛋白和和靶DNA的复合物的 冷冻电镜结构，揭示了IscB -ωRNA核糖核蛋白复合体（RNP）的详细结构，从而展示了如此小的IscB蛋白是如何与ωRNA组装并介导RNA引导的DNA切割作用。

2022年11月10日 · 2021年9月， 张锋 团队在 Science 期刊发表论文 【1】，发现了一类广泛的 转座子 编码的RNA引导核酸酶，并将其命名为 OMEGA系统（包括IscB、IsrB、Tnp8）。 其中 IscB可能是Cas9的祖先。 该研究还发现，OMEGA系统使用一段RNA来指导切割DNA双链，即 ωRNA。 更重要的是， 这些核酸酶很小，仅为Cas9的大约30%，这意味着它们可能更容易被递送到细胞中。 对于OMEGA系统， 张锋 曾表示， 对这些广泛存在的可编程核酸酶的发现感到非 …

2021年9月9日 · Using evolutionary analysis, RNA sequencing, and biochemical experiments, we reconstructed the evolution of CRISPR-Cas9 systems from IS200/IS605 transposons. We found that IscB uses a single noncoding RNA for RNA-guided cleavage of double-stranded DNA and can be harnessed for genome editing in human cells.

2016年2月12日 · The findings described here show that IscB proteins, the closest homologs of Cas9 not linked to CRISPR-Cas systems, are encoded by a distinct group of transposons, which we denote ISC. The extensive mobility of ISC transposons is supported by the discovery of numerous empty target sites in pairs of closely related genomes, one of which contains ...

2022年6月24日 · Target-adjacent motif recognition, R-loop formation, and DNA cleavage mechanisms are explained at high resolution. ωRNA plays the equivalent function of REC domains in Cas9 and contacts the RNA-DNA heteroduplex. The IscB-specific PLMP domain is dispensable for RNA-guided DNA cleavage.