For the first time, a patient has been injected with CRISPR gene-edited cells. This is just another step towards a revolutionary new era for medicine.

Once again, the news comes from China. On October 28, a Chinese team was the first to inject a patient with cells previously gene-edited using the technique called CRISPR-Cas9.

This is surely a milestone that further helps to pave the way for the era of gene editing-based medicine. But we are not there quite yet. And I think it is always important to remember that science is made of little steps rather than of big “eureka”. However, when trying focusing on the bigger picture, one can realise that we might being witnessing the revolution of medicine. But again, one step at a time. What happened in China.

A couple of weeks ago, oncologist Lu You at Sichuan University in Chengdu and his team treated a person affected by aggressive metastatic non-small-cell lung cancer with gene edited leucocytes (white blood cells). The researchers extracted the immune system’s cells from the patient and edited the lymphocytes T by turning a gene off using the well-known CRISPR-Cas9 technique, of which I talked about in other posts such as here or here. This editing system allows to programme the DNA-cutting enzyme Cas (CRISPR Associated proteins) in order to cut a specific DNA sequence.

Using CRISPR-Cas9, Lu’s team disabled the gene for a protein called PD-1, which normally regulates a cell’s immune response. Then, the modified cells were injected back into the patient’s blood stream. Hopefully, this editing will allow for a more aggressive response of the immune cells against the cancer. Although only one patient has been injected with the edited cells so far, the study is supposed to eventually treat ten participants.

At this point, I believe there are a few aspects worth considering.

This is a safety trial
It is important to underline that this is mainly a safety trial, which means that the main aim of Lu’s team is to determine whether the injection will cause any adverse effects. This will be achieved by monitoring the treated patients for several months after the injections. Indeed, since the protein PD-1 is responsible for regulating and restraining the immune response, turning it off might cause an excessive autoimmune response, in which the T cells would start attacking the body itself. Finally, as other Chinese studies showed, the CRISPR-Cas9 method tends to edit randomly out of the main target; this event is called off-target editing.

For whom is this treatment?
The trial enrols patients with metastatic lung cancer resistant to chemo and radiation therapies. However, as Naiyer Rizvi of Columbia University Medical Center in New York City pointed out, even if the therapy is successful, it will be quite difficult to reproduce it on larger groups of patients because, as he explained in Nature, “the process of extracting, genetically modifying and multiplying cells is a huge undertaking and not very scalable”.

Not exactly a “first time”
Although being the most revolutionary technique thanks to its easiness and efficiency, CRISPR-Cas9 is not the only gene-editing method used by researchers. In 2015, an 18 months-old child affected by a particularly aggressive form of Acute Lymphoblastic Leukaemia (ALL) was injected with gene-edited T cells from a healthy donor at the Great Ormond Street Hospital (GOSH). The cells had been edited using a technique called TALENs (Transcription Activator­-Like Effector Nucleases), which allowed the achievement of two goals: to make these T cells invisible to leukaemia drugs that would kill them, and to re-programme them to target leukaemia cells specifically. The treatment was unexpectedly successful.

Even earlier, in 2014, the company Sangamo Biosciences treated 12 HIV patients using T cells edited with yet another gene-editing technique based on the use of zinc-finger nuclease (ZFN). According to their results, six patients quit their antiretroviral drugs.

Another study published on 7 April 2016 in Cell Reports and concerning gene-edited T cell cultures in vitro showed that HIV can fire back. Specifically, after having ‘armed’ T cells with the CRISPR-Cas9 system to contrast the HIV infection, this team observed that just after two weeks of culture in dish the virus had developed mutations that made it resistant to the CRISPR attack. Interestingly, the team speculates that it could have been the very insertion of CRISPR-Cas9 that triggered the mutation in the first place.

The gene-editing race
Not only Chinese groups are working on applying CRISPR-Cas9 to immunotherapies. In June 2016, NIH approved an American study based on the use of this technique to editing T cells and, therefore, empowering the patient’s own immune response. This study is quite similar to the Chinese one. Indeed, some people say that this might be the first act of a ‘biomedical duel’ between China and USA.

At the beginning of this post I talked about focusing on the bigger picture. Yes, this Chinese trial is an interesting and unprecedented study, but its impact on cancer treatment might result to be rather limited. However, if we put together all the several efforts on cancer counteraction and HIV treatment it can be seen that several approaches are currently tested and each of them add a little, but crucial, piece to the great endeavour that is gene editing-based medicine.

Header image: Colorised scanning electron micrograph of a T lymphocyte. National Institute of Allergy and Infectious Diseases, National Institutes of Health via Flickr