On April 25, 2022, Prof. Hao Yin, Co-founder of CorrectSequence Therapeutics (Correctseq) was invited to attend 2022 Simcere Innovation Forum which was held in Nanjing and Boston at the same time, and made a speech titled "CRISPR-based gene therapy and nucleic acids detection". The experts from home and abroad online and offline discussed the newest technologies of biomedicine field on the forum, which abstracted about 1,500 medicine young scholars.
Prof. Hao Yin, Co-founder of Correctseq, shared his recent research results on the forum, containing the developed delivery methods, new base editing tool tBE, new prime editing tools GRAND editing. These results provided a new way to treating serious human diseases using gene editing technology.
Recently, the homologous recombination technology based CRISPR has the problem of low efficiently editing when it is used in the clinical therapy. Prof. Hao Yin’s Lab team got a nearly 100% knocking out efficiency in mouse liver using a new gene editing technology based CRISPR (Nature Biotechnology, 2017).
Prof. Hao Yin also introduced a new gene editing tools tBE (transformer Base Editor) which was developed by his lab’ team and Prof. Jia Chen, Prof. Li Yang, Prof. Bei Yang, the other three co-founders of Correctseq. The research team identified some deoxycytidine deaminase inhibitor (dCDI) domains and took advantage of mA3dCDI domains and split-TEV system to develop a novel tBE system. The tBE system remains inactive at off-target sites with a cleavable fusion of dCDI domain, thus eliminating unintended mutations. Only when binding at on-target sites, tBE is transformed to cleave off the dCDI domain and catalyzes targeted deamination for precise editing. tBE system induced efficient editing with only background levels of genome-wide and transcriptome-wide off-target mutations (tBE, Nature Cell Biology, 2021). The technology realizes precisely and efficiently editing in vivo without off-target mutations which has potential in clinical applications.
Figure 1: Dual-AAV system to deliver tBE in liver (Nature Cell Biology, 2021)
What’s more, Prof. Hao Yin’s Lab developed a new prime editing GRAND editing, which can be used to develop a new therapy to treat genetic diseases caused by mutative base gene. Through introducing a pair of pegRNAs and making a design, the researchers have developed a new prime editing GRAND editing, not only expanding the target area, but also improving the editing efficiency. The insert length of DNA by GRAND editing is 1000 bp comparing to 44bp by PE3 (GRAND editing, Nature Methods, 2022).
Figure 2: Compared with PE3 (left), the insert length of DNA is longer by GRAND editing (right)
As one of co-founders of Correctseq, Prof. Hao Yin is an expert in cell/gene therapy and drug delivery. His studies were published in Nature, Nature Biotechnology, Nature Methods, Nature Cell Biology, Nature Biomedical Engineering, Nature Chemical Biology, etc.
The scientific co-founders of Correctseq focus on the frontier of gene editing field. Correctseq uses innovative gene editing system to help people living with serious diseases. Multiple pipelines are well underway. Hope the research of Prof. Hao Yin’ Lab can transform into the clinical therapy as soon as possible, enlightening the future of people with serious diseases.
Dr. Hao Yin
Co-founder of Correctseq, Professor of Medical Research Institute and Frontier Science Center for Immunology and Metabolism (Ministry of Education) of Wuhan University. He had been the postdoc fellow of Massachusetts Institute of Technology. He received bachelor’s degree from Nanjing University and a doctorate degree from University of Colorado Anshutz Medical Campus. He was served as research scientist of Vertex Pharmaceuticals (VRTX). He has won National High-level Overseas Talent. Prof. Hao Yin is an expert in cell/gene therapy and drug delivery. His studies were published in Nature, Nature Biotechnology, Nature Methods, Nature Cell Biology, Nature Biomedical Engineering, Nature Chemical Biology, etc.