Edit genes accurately and put them in the right place. The new therapy helps patients with rare diseases.
At the end of 20 17, Brian Madeux, a 44-year-old man with rare disease hunter syndrome in California, USA, injected billions of genetic tools and correction genes intravenously in order to accurately cut his DNA. In the past, scientists edited genes in the laboratory to change human cells and then sent them back to the human body. There are also gene therapies unrelated to gene editing, but these therapies can only be used to treat a few diseases. Some therapies are ineffective for a long time, and some therapies not only can't control the position where genes are inserted into DNA, but also may lead to various derived diseases such as cancer.
But this time the gene repair is carried out accurately in the body, just like sending a micro-plastic surgeon to put the gene in the right position. "Cut your DNA, then set it, insert a gene, sew it up, and finally repair it without leaving a trace." Dr Sandy Macrae, president of Sangamo Therapeutics in California, said that the company is testing two treatments for metabolic diseases and hemophilia. "This gene therapy will become a part of your DNA and will accompany you for the rest of your life. This also means that it is impossible to edit the irreversibility of errors.
The enzyme lacking after gene therapy can be synthesized and play a normal role.
The number of people suffering from these rare diseases in the world may be less than 10 thousand, and many of them died very young. Take Ma De as an example. Hunter syndrome gene lacks enzymes that degrade some carbohydrates, which leads to the accumulation of metabolites in human body and causes harm to human body. After gene therapy, the modified gene can guide cells to synthesize necessary enzymes and play a normal role. Patients often have a series of symptoms such as colds, ear infections, facial deformities, hearing loss, heart problems, dyspnea, skin and eye diseases, bones and joints, intestinal tract and brain cognitive status. Dr Chester whitley, a geneticist at the University of Minnesota, plans to include patients in this study. He said, "Many patients with this rare disease have to be confined to wheelchairs for life and depend on their parents until they die. 」
Although this can't change the harm caused by the disease to the body, it can prevent the disease from getting worse. The corrective gene will stay in Madeux and play its due role. This study will call 30 adults to test the safety, and it is hoped that it can eventually be applied to young children to prevent serious disease injuries that have not yet occurred.
Cut DNA and allow new genes to be inserted to play a corrective role
The gene editing tool Crispr-Cas9 has attracted a lot of attention recently, but a tool called zinc finger nuclease is used in this study. They look for and cut specific DNA fragments like molecular scissors. The whole treatment process is divided into three parts: a new gene and two zinc finger proteins. Every part of the DNA instruction is stored in a modified virus, which has been changed to be non-infectious, and only uses the function of transporting them to send the tools needed for gene editing into the human body. In this case, Madeux obtained these copies by intravenous injection. After reaching the liver, the cells will use the instructions in the virus to generate the necessary tools to cut DNA and allow new genes to be inserted. Subsequently, the inserted correction gene will play a role in guiding the cell to produce the enzyme that the patient lacks. Dr. Paul Harmatz, the physician and research director of Madeux, said that only 65,438+0% of liver cells need to be corrected to successfully treat this disease.
After the controversy over the safety of gene therapy is ruled out, it is expected to bring new hope to more patients.
There are controversies about the safety of gene therapy in the early stage, such as the immune response caused by virus vectors, but this time Madeux's treatment has been proved to be safe in experiments. The second disturbing reason is that inserting one gene will have an unpredictable effect on other genes, for example, in gene therapy experiments trying to cure a rare immune system disease (called bubble boy disease). Several patients later developed leukemia because the new gene stimulated other cancer genes. So it depends on the insertion site of the new gene. If we can accurately guide and control the insertion of new genes into the correct sites, there will be no negative effects.
The third worry is whether the vector virus will bring new genes to body parts other than the target, such as the heart, or even into eggs or * * *, causing the next generation. But doctors say that because of the gene protection mechanism, new genes will only be inserted into liver cells, just as seeds will germinate only under certain conditions. Mado was treated in Oakland Hospital, California. After one month, there will be signs of therapeutic effect, and after three months, the curative effect will be tested and confirmed. If this therapy is successful, this new technology will bring great progress to the field of gene therapy. As the first human to receive gene therapy in vivo, Maddex felt full of hope. Although this can't change the harm caused by the disease to the body, it can prevent the disease from getting worse. The corrective gene will stay in Madeux and play its due role. If this treatment is successful, it will greatly promote the development of gene therapy. Because the insertion site of the new gene can be accurately controlled, the safety and effect of treatment will be improved. If the treatment is extended to other genetic diseases, it will bring hope to more patients.
refer to
Guardian/Science /2065 438+07/ 1 1 month/15/ Scientists try to edit genes in vivo for the first time.
Subject: gene therapy, gene editing