Gene therapy: what else do we need to do to treat human patients?

What does gene editing mean for the biomedical industry? In the new decade, what changes will it usher in? We know that sunlight, smoking, unhealthy diet, even spontaneous cell errors can cause our genome to change Dr Liu Ruqian pointed out that 75000 mutations have been found to be related to human diseases, the most common of which is single base point mutation For example, known as sickle cell anaemia, a to t point mutation occurs In addition, genomic changes include base deletion and insertion For example, the most common cause of cystic fibrosis is the loss of three bases, while the most common cause of Tay Sachs disease is the insertion of four DNA letters "So far, there are at least 6000-10000 known genetic diseases related to gene mutations In order to truly solve the causes of disease, we need to develop methods to correct or improve gene mutations." Gene editing has developed rapidly in recent years, thanks to the breakthrough of CRISPR technology Six years ago, several gene editing pioneers, including Dr Emmanuelle Charpentier, Dr George church, Dr Jennifer doudna and Dr Zhang Feng, showed us the elegance and beauty of CRISPR gene editing technology CRISPR's most amazing feature is that the gene editing scissors can receive human programming instructions, only search, bind and cut specific DNA sequences, including human genome sequences Because of its high efficiency, convenience and wide range of application, CRISPR technology breakthrough makes the development of genome editing enter the fast lane, scientists, doctors and patients all over the world are very excited In many cell types, cutting the DNA will lead to the destruction of the therapeutic gene, so it is expected to become a potential therapeutic method ▲ Dr Liu Ruqian "In many cases, however, we do not want to destroy the pathogenic genes Instead, we need to precisely repair mutations that lead to genetic diseases " Dr Liu Ruqian said that there are hundreds of diseases in the world To treat them, we only need to restore the gene to the wild-type state, and there is no need to do gene knockout For example, if we want to treat sickle cell anemia patients by directly correcting hemoglobin mutation, we can not simply cut off the hemoglobin gene, which will lead to further damage The best way is to be able to repair the mutation For this reason, Dr Liu Ruqian's research group has developed a new gene editing method called "single base editing method" For example, if crispr-cas9 technology is the "scissors" of the genome, then the single base editing method is "pencil and eraser", which can erase and rewrite a letter in the gene This technology can complete the precise editing of genes without breaking DNA Single base gene editing has opened the door of precise gene editing, and also been selected as one of the breakthroughs in 2017 by science magazine Although a big step has been taken towards accurate gene editing, there is still a lot of room for development of this technology Single base editing can "fine tune" point mutations, but it is not suitable for modifying large segments of genes In addition, there are 12 ways to change one base to another, while this single base editing scheme can only be modified by four ways (for example, t cannot be changed into a) For this reason, Dr Liu Ruqian's team has conducted further research At the end of 2019, the team newly reported a new CRISPR gene editing technology called "prime editing" The leading editor is called a "molecular word processor", which can find one strand in DNA molecule and replace it directly with another At present, this gene editing technology has been authorized to prime medicine company for development, aiming at early application to patients Dr Chen Zhisheng and Dr Liu Ruqian discussed technological uncertainty and medical ethics According to Dr Liu Ruqian, researchers do not have enough foresight to predict the adverse effects when choosing the target of gene editing Therefore, it is urgent to introduce as many innovative regulatory mechanisms as possible From the perspective of ethics, from the perspective of society, this is crucial to ensure that the ongoing gene editing experiments are concerned by the whole society At the same time, Dr Liu Ruqian doesn't need to worry too much about the side effects of gene editing In fact, every molecule entering the human body will have miss target activity, which is one of the main side effects of genome editing First of all, molecular binding has never been completely specific, which is physically impossible Whether it's small molecule chemicals, antibodies or genome editing therapy, they will be combined with non target Secondly, we have no way to detect the binding position of aspirin with proteome or genome, but we have been able to detect the changes of genome caused by gene editing At present, many laboratories have developed a method to accurately predict the whole genome for Miss editing Even at a very low level, the burden of mutation caused by unnecessary gene editing can be reduced as much as possible Dr Chen Zhisheng Dr Chen Zhisheng raised several issues of special concern in the industry - how gene editing technology can achieve value for patients, and how FDA views the new technology Liu recalled that a few years ago, Dr Francis Collins had organized a conference on gene editing to promote the development and application of technology At that time, the field of gene editing was still in the stone age or bronze age "In just a few years, the field of gene editing continues to explode with innovative editing capabilities, redefining the potential boundaries of gene editing, and expanding the goals we can pursue in gene editing." Said Dr Liu Ruqian happily In 2019, CRISPR gene editing technology has gone from laboratory to clinic Editas announced the launch of the world's first in vivo CRISPR gene editing clinical trial, which will use a CRISPR based gene editing therapy for Leber's congenital amaurosis 10 (lca10) patients In terms of gene editing in vitro, CRISPR therapeutics also announced a 1 / 2 phase clinical trial to obtain positive interim data: a transfusion dependent β - thalassemia (TDT) patient and a severe sickle cell anemia (SCD) patient received ctx001 treatment and achieved the effect of stopping transfusion dependence In 2018, Professor Liu Ruqian also co founded a company called beam therapeutics, which uses revolutionary single base gene editing technology to develop precision therapy, with a view to early application to patients It is worth mentioning that this is also the first company to develop a new therapy using CRISPR single base editing technology Beam currently has 12 research projects in the treatment of β - thalassemia, sickle cell anaemia, acute lymphoblastic leukemia (all) and acute myeloid leukemia (AML), as well as liver diseases and eye and central nervous system diseases In 2017, we witnessed the birth of the world's first gene therapy, known as the first year of gene therapy Up to now, FDA has approved four gene therapies, two of which are car-t cell therapy for blood cancer, the other two for hereditary retinopathy (luxturna, spark, 2017) and spinal muscular atrophy (zolgensma, Novartis / avexis, 2019) And Dr Liu Ruqian pointed out that gene editing may bring breakthroughs in the next generation of gene therapy "Every gene editing tool and therapy will find room to play," he said Each of these therapies has its own strengths and weaknesses, whether it's gene editing, gene amplification, or cell therapy These technologies are also different Our responsibility is to try our best to play the role of each technology and treat as many patients as possible " (Note: the original text has been deleted) Original title: gene editor: are we really ready to treat human patients? |Wuxi apptec Global Forum A kind of