The research progress and development of base editing is new.

On April 18, Yang Li, a researcher at the Shanghai Institute of Nutrition and Health of the Chinese Academy of Sciences, and Chen Jia, a professor at the School of Life Technology at Shanghai University of Science and Technology, and Yang Bei, an associate researcher at the Institute of Immunochemistry of Shanghai University of Science and Technology, were invited to publish a commentary on the news and views of To Be or Not to BE, that is the question, in the international academic journal Nat Biotechnol.
in recent years, a new base editing system (Base Editor, BE) developed using crispR/Cas9 gene editing systems integrated with nucleoside deaminase, including cytosine base editor (Cytosine Base Editor, CBE) for C-to-T editing, and adenine base editor (Adenine Base Editor, ABE) for A-to-G editing, which enables accurate and efficient genome editing at the monobase level.
this new base editing system, theoretically will not cause double-stranded fracture damage to genomic DNA, and can be targeted to correct thousands of genomic base mutations that cause human diseases, so it has a wide range of clinical applicationprospects.
However, two recent studies published in the journal Science show edited that be3, an early-constructed cytosine base editor, can cause more nonspecific mutations than Cas9 in the genomes of mouse embryos and rice than traditional Cas9, and that the production of these nonspecific mutations does not depend on the specific guidance of sgRNA (Zuo et al., 2019, science; Jin et al., 2019, Science; Jin et al., 2019, Science; Kim et al., 2019, Nat Biotechnol.
Although the mechanism of BE3 causing nonspecific mutations is not reported in detail in the above-published study, in this news and perspective article, Chen Jia and others speculated that the cytosine deaminase in BE3 may have an unexpected off-target effect through a cytosine deamin reaction that does not rely on sgRNA-mediated;
finally, the paper also points out that the cytosine base editor, based on low-activity cytosine deaminase, may not be effective in mediating genomic targeted base editing in tissue organs or somatic cells (such as progenitor blood cells).
therefore, how to develop a new strategy to build a low-target ingline editing system will become the future development of the base editing field of difficulties and breakthrough points.
diagram: A comparison of genes mediated by Cas9 and base editor BE3.
a, Cas9-mediated gene editing with its activated DNA damage response.
b, BE3 mediates base editing at sgRNA-dependent target sites and off-target sites.
c, BE3 mediates base editing at sgRNA non-dependent off-target site.
Yang Li has been engaged in the analysis and research of material information of many groups of students for a long time.
recently worked with The Chen Jia Team of Shanghai University of Science and Technology, the Huang Xingxu Team and the Yang Bei Team to illustrate the molecular mechanism of mutations produced by APOBEC in the repair of genomic DNA fractures caused by CRISPR/Cas9 (Lei et al., 2018, Nat Struct Mol Biol), and successfully created a new type of base editing system (Wang et al., 2017, Cell Res; Li et al., 2018, Nat Biotechnol; Wang et al., 2018, Nat Biotechnol.
Source: Shanghai Institute of Nutrition and Health.