A Rundown on CRISPR Clinical Trials

1. Cancer

Results from a phase one clinical trial using CRISPR to treat cancer have been posted (NCT03399448). Specifically, a CRISPR-based therapy was used in patients with melanoma, multiple myeloma, synovial sarcoma, and cell liposarcoma. The researchers took the patient's immune cells, edited them in the laboratory, and then these CRISPR-edited cells were infused back into the patient. The CRISPR-edited cells were developed to have a specific receptor that can help to find and remove cancerous tumours in the body, thereby improving the immune system to fight cancer. The primary aims of the study were to assess the safety and feasibility of producing the CRISPR-edited T cells.

The results of the clinical trial seemed positive. According to the researchers, the CRISPR therapy is safe to use in patients, and interestingly the cells have long term functionality. "Previous studies have shown these cells lose function within days, so the fact that the CRISPR-edited cells in this study retained anti-tumor function for a significantly longer period of time after a single infusion is very encouraging,” said MD Carl June, professor in immunotherapy, in the Penn Medicine News Press Release.

2. Sickle-cell disease

There is a clinical trial using CRISPR editing for the treatment of severe haemoglobinopathies such as sickle cell disease (NCT03745287). The clinical trial is a collaboration between CRISPR Therapeutics and Vertex Pharmaceuticals that began way back in November 2018. In this study, the patient's cells are taken and edited with CRISPR to increase the production of fetal haemoglobin, and then finally, the cells are infused back into the patient. The researchers hypothesised that the fetal hemoglobin would be able to reduce the complications of the sickle haemoglobin.

In a press release back from November 2019, the CEO of CRISPR Therapeutics, Samarth Kulkarni said: "We are very encouraged by these preliminary data, the first such data to be reported for patients with beta-thalassemia and sickle cell disease treated with our CRISPR/Cas9 edited autologous hematopoietic stem cell candidate, CTX001."

According to the researchers, the patients were producing fetal haemoglobin, and this helped to reduce the number of vaso-occlusive crises and the number of blood transfusions required by the patients. In June, new data for this CRISPR-based therapy will be presented at the 25th European Hematology Association (EHA) Congress. The presentation will showcase the long term effects of using this CRISPR-based therapy which will be very interesting to hear about, fingers crossed it is a positive result! Furthermore, the patients that participated in the initial trial have been invited to participate in a long term clinical trial that is estimated to finish September 2039!! (NCT04208529)

3. HIV

A clinical trial based in China was using CRISPR editing to treat HIV (NCT03164135). The researchers were using stem cells from a donor and editing these cells with CRISPR to disrupt the CCR5 gene, and then these cells were infused into the patient. HIV uses the CCR5 receptor found on our white blood cells to gain entry to our cells. People with a mutation in the CCR5 gene have immunity against some strains of HIV, as the mutation alters the CCR5 receptor, and thus prevents HIV from entering their cells. The aims of this study were to assess the safety of this therapy and then to measure the number of CRISPR-edited cells that were able to persist in the patient's samples and whether the patient experienced any resistance to HIV.

Results from this clinical trial were posted in The New England Journal of Medicine. It was found that a bit over half of the CRISPR-edited cells had died, but some persisted in the patient for more than 19 months, and there were not any severe complications as a result of the gene-editing. Furthermore, the viral load had not reduced enough, and subsequently, the patient still has HIV. Therefore, showing that this therapy still needs to be improved so that it can reduce the viral load but it does have potential long term capabilities.

4. Leber congenital amaurosis

A clinical trial using CRISPR to treat blindness caused by Leber congenital amaurosis 10 is currently being conducted in the US, it is a collaboration between Allergan and Editas Medicine (NCT03872479). The researchers want to determine the safety and effectiveness of the CRISPR treatment and whether the patients can tolerate the CRISPR therapy. In a first, the treatment will be injected directly into the patient's eyes, this therapy works by correcting the disease-causing mutation on the CEP290 gene. Now we just await the results for this exciting clinical trial, the study is estimated to finish around March 2024.

Due to COVID-19, there will likely be a delay in the clinical trials mentioned in this article.