Recently, Dr. Xiaodun Mou, CEO of CorrectSequence Therapeutics, visited the "Dialogue 22" column of Oriental Financial Pudong Channel to share how to use creative gene editing technology to develop low-cost and high-quality therapy for people with severe diseases.

"Gene editing is to find the mutated genes from the ontology DNA, and then use a fast and efficient method to correct the mutated genes to healthy genes as expressed as normal people, and then let the patient back to the normal growth track through the body's own regulation and growth function." Dr. Xiaodun Mou first introduced what gene editing is.

Gene editing technology can fundamentally solve some difficult diseases that have not yet found effective therapy, such as genetic diseases or chronic diseases. It will bring new hope to patients with these diseases. Currently, these diseases brings huge financial burden and psychological pressure to patients because there are no cure or only some symptomatic chronic treatments. 

Dr. Xiaodun Mou introduced, gene editing technology has been developed for nearly 30 years, from ZFNs, TALENs, to the CRISPR/Cas9 technology, the generations of gene editing technology are known as "molecular scissors", its common characteristic is to repair genes by completely cutting off the double strand break of DNA, which will bring about clinical risks such as large fragments chromosome deletion and chromosome translocation. "It's like being shot in the heart, the normal reaction is that the person dies. Normal human cells also have a mechanism to protect the body. If its DNA double strand is cut off, the cell will die, and then a replication error will occur when it copies itself. Chromosome abnormalities are the cause of many deadly diseases in humans, especially cancer, where cells with abnormal chromosomes can become tumors if they frantically copy themselves." Dr. Xiaodun Mou said that although the" molecular scissors " technology such as CRISPR is very convenient, there are still many safety risks in the human body.

In order to improve the editing efficiency and security, the scientific founders of Correctseq developed base editing system represented by tBE (transformer Base Editing) , it induces precise base substitutions to achieve genome editing through combining two moieties, "effector" and "locator". "transformer Base Editing (tBE) does not cause any damage to the DNA double strand, it just makes an unspiral motion, creating a very small "O" shaped window. As you can imagine, a playground full of people, maybe we only open one cell of one person, so the effect on the human body is basically negligible. " Dr. Xiaodun Mou vividly introduced the principle of tBE and its safety and efficiency. After unwinding the helix, the system delivers another deaminase into the body, precisely making the C-to-T or A-to-G transition. Base editing technology does not cause damage to the DNA double strand, so it effectively avoids the risks of promoting the activation of p53 pathway and chromosome abnormalities, and realizes the precise repair of "turning a scissor into a pen". Compared with previous generations of gene editing technology, base editing technology has substantially improved its safety and drug properties in the application of human disease treatment.

Correctseq is developing the base editing technology into gene editing therapies for clinical application. At present, Correctseq has established target screening, Pre-IND and CMC platform in line with international drug regulatory standards, and successfully constructed and expressed tBE using mature molecular types and CMC processes. Animal studies have been carried out through ex vivo cell editing and in vivo delivery (LNP and AAV), and the safety and efficacy have been verified. At the same time, tBE has demonstrated its powerful potential in a wider range of diseases. These disease areas include rare diseases, T cell engineering, infectious diseases, and immunooncology. tBE has demonstrated high editing efficiency for potential targets without any off-target phenomenon.

Correctseq has gathered dozens of outstanding biomedical experts from the fields of R&D, new drug development, CMC development, clinical operation, quality, etc. The management team and R&D team have more than 10 years industrial experience, with more than 40% of the staff holding doctoral degrees. The team will make use of the previous experience in the pharmaceutical of biological innovative drugs, combined with the regulations and norms of National Medical Products Administration, comprehensively consider the quality, cost, supply chain and other factors of drugs, shorten the process of new drug research and development and clinical entry, ensure the high quality of drugs while considering cost control. The company plans to push the first pipeline into the IND application phase next year.

At the same time, Correctseq has owned and is continuously applying for patents on various new drug targets, such as blood, tumor immunity, infectious diseases and metabolic diseases, which will effectively reduce drug costs. Correctseq also looks forward to sharing base editing technology with more partners to expand the application of this technology. In the future, base editing technology can be applied not only to genetic diseases, rare diseases, but also to common diseases, benefiting more patients around the world.