On Aug 2-4, 2022, National Medical Products Administration Institute of Executive Development hold Drug Researcher Conference online. Dr Lijie Wang, head of CorrectSequence Therapeutics (Correctseq) Gene Editing Platform, was invited to attend the conference and made a speech on the topic of “the Latest Advances and Clinical Applications of Gene Editing”. (Online Live| Drug Researcher Conference( Topic: Biologics Registration Regulations and Applications)
Dr. Lijie Wang introduced the history of base editing, the advantages of new gene editing therapy and compared the exiting gene editing tools. tBE(transformer Base Editor), which is created by Correctseq’s scientific co-founders, can not only edit precisely and efficiently without off-target mutations, but also deliver efficiently in vivo and ex vivo with AAV, mRNA/lNP and other delivery methods. Dr. Lijie Wang also shared the clinical case of gene editing in vivo and ex vivo and the future development potential of gene editing therapy.
Figure 1 Comparison of Gene Editing Tools
As the new star of gene editing area, base editor can correct one base gene precisely through editing without making double-strand DNA break. But there are many problems to be solved such as avoiding off-target mutations, expanding target area, improving editing and delivering efficiency in vivo, etc.. tBE is created to solve these problems. Through a clever “lock”, tBE edits only when it is in the correct target. If it is on the wrong target, tBE can’t edit normally. The experimental data proves that compared with Cas Nuclease gene editing therapy, tBE exhibits higher editing efficiency and γ-globin induction, lower cytotoxicity and no off-target mutations.
Figure 2 Undetected Off-target Mutation by tBE
Dr. Lijie Wang said that gene editing technology can used in many disease area and there are several gene editing therapies in vivo and ex vivo with IND in the whole world. tBE can be used to create new gene editing therapy for eye diseases, cardiovascular disease, genetic disease, etc.. It gives the hope of “once treatment, lifelong cure” because of its advantages of precisely editing, off-target mutation and delivering with AAV, mRNA/LNP and other delivery methods.
Figure 3 Clinical Applications of Base Edit Technology
tBE has the potential to transform into new gene editing therapies in the future. We can use base editing technology to correct the mutated gene which causes some kind of disease, knockout the target gene through introducing stop codons, realize multi-target editing through editing two or more target genes. Correctseq’s first IND pipeline CS-101 is for thalassemia, which uses tBE to developing a creative gene editing therapy. Compared with Cas Nuclease gene editing therapy, tBE exhibits higher editing efficiency and γ-globin induction, lower cytotoxicity and no off-target mutations. New therapeutic targets and new drug pipelines are under independent development by Correctseq. Nearly 10 pipelines for genetic diseases, tumor immunotherapy, metabolic diseases, and infectious diseases are well underway.
Correctseq aims to use our innovative gene editing system to help people living with serious diseases. In the future, Correctseq will support National Medical Products Administration Institute of Executive Development in training drug researchers as usual and help promote Chinese biomedicine to the world stage, provide efficient, reliable and safe solution for patients worldwide.
Dr. Lijie Wang
Head of Gene Editing Platform, Director of R&D in CorrectSequence Therapeutics. She received Bachelor’s degree from Southern Medical University and a doctorate degree from ShanghaiTech University. She has won the National Scholarship Award, Graduated with honor of Shanghai, Graduate Principal's Award of ShanghaiTech University. Dr. Wang is co-first inventor of eBE&tBE. Her research focuses on the development and application of the innovative gene editing tools, leading the construction of transformer base editors (tBE) and enhanced base editors (eBE), which was published in Nature Cell Biology, Cell Research, etc.