CRISPR/Cas9: The first clinical trial

In China, for the first time, the genome of an adult was modified using CRISPR

Sofia Dolotovskaya, N+1

For the first time in the world, Chinese scientists conducted an experiment on editing the genome of an adult using CRISPR/Cas9 technology. On October 28, a patient with lung cancer was injected with modified T-lymphocytes. The experiment is reported in the editorial Nature (David Cyranoski, CRISPR gene-editing tested in a person for the first time).

Clinical trials for the treatment of lung cancer using CRISPR-modified T-lymphocytes, conducted by employees of Sichuan University, were approved in July 2016. The first experiments were supposed to take place in August, but the start of the tests was postponed because cell culture took longer than planned.

As part of the trials, patients with metastasized non-small cell lung cancer resistant to other types of treatment are injected with their own T-lymphocytes, in which the PD-1 membrane protein gene was removed using CRISPR/Cas9 technology. This protein suppresses cellular immunity and allows the tumor to inactivate lymphocytes. Currently, antibody-based drugs are used to block this protein, but the response to them is very different in different patients. Scientists hope that the effect of using CRISPR will be more pronounced and predictable.

According to the head of the trials, the infusion of T-lymphocytes to the first patient was successful, and soon he will be injected with a second dose of modified cells. If this first patient does not have pronounced side effects, the number of subjects with metastasized non-small cell lung cancer will increase to 10. They will be injected with different doses of modified T-lymphocytes during 2, 3 or 4 infusions. Within 6 months after that, patients will be monitored to check whether the infusions cause side effects. Observations of the results of therapy will continue later.

Trials on editing the human genome using CRISPR/Cas9 technology are also planned in the USA. So, in June 2016, the US Federal Commission on Biosafety and Ethics approved clinical trials in which this technology will be used to make additional changes to T-lymphocytes with chimeric antigen receptors (CAR). It is planned to remove the PD-1 protein in the cells, as well as the natural TCR lymphocyte receptor, the presence of which reduces the effectiveness of CAR. If the commission's decision is supported by the U.S. Food and Drug Administration (FDA) and the ethics committees of medical centers, clinical trials may begin in early 2017. A little later, in March 2017, a group of researchers from Peking University also hopes to launch three clinical trials in which CRISPR/Cas9 technology will be used to treat bladder, prostate and renal cell carcinoma. These tests, however, have not yet been approved and have not received funding.

The CRISPR/Cas9 system has been found in the genome of bacteria, where it plays the role of antiviral protection. This system allows you to edit the DNA of an organism in a targeted way without affecting the rest of the genome. Cas9 endonucleases cut the DNA in the right areas, complementary to the "template" of the RNA guide, after which the cell's own repair systems stitch the ends of the DNA, fixing the changes. Previously, CRISPR/Cas9 technology was tested, for example, for the treatment of beta-thalassemia in human embryos, the removal of HIV genes from infected lymphocytes and the treatment of sickle cell anemia.

Portal "Eternal youth" http://vechnayamolodost.ru  17.11.2016