CRISPR-Cas9 gene therapy has been shown to be effective in vitro, although until now the gene editing technique has not been used in vivo in humans. However, a group of oncologists in China have now used CRISPR-Cas9 edited cells to treat a patient suffering from an aggressive form of lung cancer – metastatic non-small-cell lung cancer.
CRISPR-Cas9 gene therapy uses a combination of guide RNA (gRNA) which binds to a specific section of DNA and a Cas9 enzyme to cut the DNA at a specific point. Sections of the DNA can be removed or added as necessary. The CRISPR-Cas9 gene therapy technique has been tested in animal studies and on human cells in vitro, but until now, the CRISPR-Cas9 technique has not been used to treat diseases in vivo.
Trials has been planned in the United States, although they are not scheduled to commence until early 2017. The U.S. trials will involve the use of CRISPR-Cas9 gene therapy on three genes and the trials will involve patients suffering from terminal cancer. Further trials on cancer patients have been proposed in China although they are currently awaiting funding.
The first CRISPR-Cas9 clinical trial was conducted on October 28 in the West China Hospital in Chengdu with oncologist Lu You of Chengdu’s Sichuan University leading the trial.
Immune cells were extracted from a blood sample taken from the patient. The CRISPR-Cas9 gene therapy technique was then used to disable the gene responsible for triggering the synthesis of the protein PD-1. The PD-1 protein usually slows the immune response. When the immune response is suppressed, cancer cells proliferate quickly.
The gene-edited cells were then cultured in vitro to increase their number and they were injected back into the patient. The aim of the trial was to prevent the synthesis of PD-1, thus allowing the patient’s immune system to attack – and hopefully defeat – the cancer.
The clinical trial was approved by the hospital review board in July and was scheduled to take place in August, although the trial was delayed as the team experienced difficulty culturing and amplifying the cells for the procedure.
The procedure went as planned and further injections will be performed, with the patient scheduled to receive three or four injections of the modified cells. A further nine patients will also be treated as part of the trial.
The main aim of the study is to demonstrate whether the technique is safe for use in humans. The patients will be monitored over a period of six months to see how they respond and whether there are any negative effects associated with the treatment. Patients will be continuously monitored after the six months to determine how well they respond to the treatment and whether there is any effect on the growth of cancer cells.
Whether the technique proves to be more effective than the use of antibodies to neutralize PD-1 remains to be seen. Regardless of the outcome, this is certainly a major milestone in the use of CRISPR-Cas9 gene therapy.