Scientists who have created and developed CRISPR constantly show the world the revolutionary breakthroughs of life science in the past ten years. On March 25, experts from the academia and investment gathered at the 26th SDDA Forum to focus on the cutting-edge scientific and technological achievements of CRISPR technology which is expected to overcome stubborn diseases and discuss the new industrial direction of gene editing field.

the 26th SDDA Forum  Guests Group Photo

Turning a Scissor into a Pen, Base Editor Rewrites "Four-character Book"

The human life codes composed of four bases are huge and complex. CRISPR is expected to correct the wrong genetic information of life codes as "molecular scissor". When the key element Cas endonuclease cuts off DNA, DNA repair mechanism will be triggered (Homologous recombination, HR or Non-homologous end joining, NHEJ) to recombine the broken DNA chains, and DNA modification and editing is realized. Because of this repair response, "molecular scissor" can have broad application scenarios and therapeutic potential. In 2016, a team of Qianru (David) Liu from Harvard used the CRISPR system to build a permanent and efficient base editor (converting cytosine to thymidine, or converting guanine to adenine), which was selected as one of top 10 scientific breakthroughs of Science the following year.

In the forum keynote speech, co-founder of CorrectSequence Therapeutics, Dr. Jia Chen described base editor as a "pen", "base editor using Cas protein recognition and binding ability to edit (currently can edit 2-3 genes at the same time) by connecting nucleoside deaminase or even reverse transcriptase, not only greatly improves the efficiency of CRISPR base editing, but also mechanically avoids double-stranded break in DNA and reduces the risk of activating downstream DNA damage-response pathway.”

Combined with deaminase, reverse transcriptase suitable for different bases, and various localized proteins including Cas9 and Cas12a, etc., researchers have developed dozens of editors for various base conversion paths. The editing system based on the research results of Professor Ruqian Liu, significantly expands the identification range and editing accuracy and efficiency of CRISPR to target genes, while reducing by-products and improving safety. Dr. Chen said, "Recently new technologies have emerged, such as AI prediction CRISPR target sequence editing ability, mitochondrial DNA editing, genome-wide mutation screening. However, considering the clinical application, we firstly focus on the precise base editing of DNA in the nucleus, and constantly develop gene editing and create innovation gene therapies.”

Personalized Drug Delivery Gains Momentum, Gene-editing Therapy Has a Bright Future

In the interactive session, speakers and audiences discussed the application of CRISPR technology in the treatment and detection of various diseases. At present, the therapies based on CRISPR technology have made positive progress in the treatment of genetic or rare diseases, including thalassemia, sickle cell anemia and congenital dark, and entered clinical trials. Due to the special physiological characteristics or drug delivery characteristics, the editing and treatment of pathogenic gene loci of related diseases of tissues such as liver, eyeball and brain, show more optimistic clinical application prospects. The delivery modes of new gene editing tools such as adeno-related virus optimization, dual-vector delivery, and lipid nanoparticles are also the personalized drug delivery design in the CRISPR 2.0 era.

In addition, COVID-19 detection reagent, HIV long-acting slow-release ART therapy, T cell and NK cell therapy based on CRISPR technology have been urgently authorized by the FDA for use or to enter into clinical trials. In response to the expanding tool innovation and indications, Dr. Jia Chen said, "At present, the application scenarios of RNA editing using CRISPR technology are very different from DNA editing. In addition, due to the rapid proliferation of cancer cells, once a few cells are not successfully edited, it may still lead to tumor recurrence, so there are still challenges to cure cancer by directly correcting the mutated genes. Therefore, we hope to start our work from the genetic diseases suitable for gene editing therapy, and then explore a wider space.”

Focus on Academia, Pursue the Future Industrial Innovation Research and Development

In addition to the keynote speech, Chen Wen, a partner of Yonghua Capital, hosted a thematic discussion between scientists, entrepreneurs and pharmaceutical investment institutions in the forum. Everyone reviewed the evolution of biomedicine in the past ten years, and believed that the industry has built an "infrastructure" system for pharmaceutical R&D, and now the focus of the capital has changed from the fast-following R&D model to the independent cutting-edge technology. Gene editing and nucleic acid therapy are hot topics in the industry.

In addition to the keynote speech, Chen Wen, a partner of Yonghua Capital, hosted a thematic discussion between scientists, entrepreneurs and pharmaceutical investment institutions in the forum. Everyone reviewed the evolution of biomedicine in the past ten years, and believed that the industry has built an "infrastructure" system for pharmaceutical R&D, and now the focus of the capital has changed from the fast-following R&D model to the independent cutting-edge technology. Gene editing and nucleic acid therapy are hot topics in the industry.

Yang Shujun, vice president of Legend Capital, said, "CRISPR is a hot track for academia and investment, but there are still many challenges from avoiding off-target risks, drug delivery efficiency to large-scale formulation production. Faced with the rapid development of nucleic acid therapy, enterprises and talents with mature R&D and commercialization model are scarce around the world. Academia has a clear first-mover advantage in-depth knowledge of this field. Transforming the academic research into products with the help of industry power is the important logic and value for VC to invest in biotechnology company.”

Dr. Lu Qiang, executive chairman of SDDA and Genfleet, thanked the investment and industry jointly meet the challenges and opportunities in the most cutting-edge technology fields. "In the past ten years, SDDA has witnessed the vigorous development of innovative drug in China and the growth of many biotechnology enterprises in Zhangjiang Pharmaceutical Valley. We look forward to the entrepreneurial talents in academia and industry, constantly transforming CRISPR technologies and more cutting-edge technologies into disease therapies, and pursuing the dream of global biological innovation research and development!

Dr. Danyi Wen, chairman of LIDE Biotech, issued a corporate membership certificate to Kactus Biosystems