How does CRISPR gene editing work?

What does the application of gene therapy look like in practice? Adrian Thrasher is a professor at UCL, and a little over 20 years ago, he pioneered the use of viruses as a means of delivering gene therapy to sufferers of ADA deficiency, a genetic metabolic disorder that causes immunodeficiency. This treatment proved successful, showing that gene therapy can transform lives, but there are risks doing this with viruses. Therefore, if we can edit genes more safely and discreetly, as happens with CRISPR, then that is safer...

Adrian - We can identify the genes that are involved in causing a disease using conventional sequencing methods. Once we know that we can decide to treat the patients using synthetic genes which were conventionally delivered using vectors such as lentiviral vectors which will deliver the genes randomly throughout the genome. Or more recently technology has advanced so we can now use CRISPR to more precisely correct the defects within the cells.

Will - So what does that procedure involve?

Adrian - For the patient what it means is that we can remove the stem cells in the bone marrow and modify those in a laboratory in a sort of clinical grade laboratory and then give them back to the patient. Now that sounds very simple but there are a few nuances to that because the technology to introduce the genes into the cell or the CRISPR into the cell is fairly complex and also the treatment of the patient to enable them to receive the gene corrected cells is also complex. For example it may involve giving some chemotherapy to eliminate the diseased bone marrow before giving back the corrected bone marrow.

Will - So the idea is because bone marrow is where all new cells are made, if you can pop your new good gene cells in there, they'll administer themselves appropriately out into the body?

Adrian - That's exactly right. So the bone marrow has some very specialised cells called haemopoietic stem cells which live within the bone marrow. They divide and create more stem cells but more importantly they populate the whole body with all the blood lineages that we're familiar with. So red blood cells, white blood cells and platelets.

Will - How long does it take for these new engineered cells to sort of have an effect?

Adrian - Well it's variable it depends on the disease that's being treated but, very similar to a bone marrow transplant where another person's cells are used to correct a disease, It takes time for the stem cells to engraft and then repopulate all the lineages in the blood and so that usually takes a few months.

Will - CRISPR is as we keep repeating in this programme pretty cutting edge so it probably doesn't have the track record of other types of gene editing when it comes to treating genetic diseases but if we look at a few of its predecessors what kind of genetic diseases have been involved in treating with this method?

Adrian - Some of the haemoglobinopathies, so sickle cell disease, has been treated using CRISPR. There are big efforts to try and use it in other haemoglobinopathies and immune deficiencies such as ADA deficiency which we know is treatable by gene therapy using lentiviral technology, gene addition technology, and therefore it will make it amenable to CRISPR based technologies, which hopefully will make it a more accurate fix to the cells and therefore safer for the patients.

Will - Do you foresee many more genetic diseases being able to be treated with these means?

Adrian - Yes absolutely because you know in theory you could target any genetic disease using CRISPR or CRISPR-like technologies. The issue which has been the issue for all gene therapies is how do you deliver the therapeutic agent to the cells that you want to correct? Now for bone marrow it's relatively easy because we can take the bone marrow out of the patient and modify it in the lab. For other diseases we may want to deliver the CRISPR to organs in the body and that may be more difficult but in theory yes many many genetic diseases will be amenable to this sort of treatment.