Just 13 years after the CRISPR gene-editing technique was described, the first medical treatment to make use of it has been approved. On 15 November, effectively cure sickle cell disease and transfusion-dependent beta thalassemia for people aged 12 and over. The US and European Union are expected to approve it soon too.
It is a momentous step forward 鈥� and it is just the start. The treatment, called Casgevy, is based on a first-generation CRISPR technique. Improved versions of CRISPR already being tested in people promise to be safer, cheaper and more effective. Meanwhile, some researchers are trying to create even better gene-editing tools that could make CRISPR redundant.
If these efforts succeed, gene editing could soon be used to treat and prevent many common conditions, such as heart disease, as well as inherited ones. It is also probably the best hope for greatly extending our healthy lifespans and is already helping to treat some cancers.
Advertisement
Researchers had developed several gene-editing techniques before CRISPR, but creating the necessary tools was extremely difficult and expensive. The problem lay in the first step: finding the bit of DNA you want to change.
Early gene-editing techniques required proteins to be designed with the right shape to bind to specific DNA sequences. With CRISPR, the editing protein remains the same, finding the desired target with the help of a 鈥済uide RNA鈥� with a matching sequence.
Because RNAs are cheap and easy to make, thousands of labs worldwide were able to start using CRISPR. However, the standard form is more of an eraser than an editor. CRISPR鈥檚 Cas9 protein just cuts DNA at a specific site and when the cell tries to repair the cut, it introduces mutations.
鈥淭he native function of CRISPR is to destroy, not to edit,鈥� says at Columbia University in New York, who was not involved in research related to CRISPR for sickle cell disease or beta thalassemia.
But destruction can sometimes cure. Sickle cell disease and beta thalassemia are caused by mutations in the adult form of haemoglobin, the oxygen-carrying protein in our blood. Casgevy works by destroying the 鈥渙ff switch鈥� that halts the production of fetal haemoglobin as we get older.
The treatment involves removing blood stem cells from the body, editing them and replacing them. This removal is done for two reasons.
Firstly, we still lack effective ways to deliver CRISPR machinery to a high enough proportion of specific cell types in the body, such as blood stem cells. Secondly, when cells are edited outside the body, some checks for potentially dangerous unwanted mutations can be done before reimplanting them.
The downside is this is very expensive, because of all the hospital visits and lab time required for personalised treatments. The ideal would be an off-the-shelf treatment that can be given as an injection to anyone with a certain condition, editing only the cell types that need altering and making specific edits without introducing random mutations.
That means not relying on cells鈥� repair mechanisms to do the editing. 鈥淲e need tools where all the components of the gene-editing process are under our control,鈥� says Tang.
The good news is that we are already part of the way there. Modified forms of CRISPR known as base editing and prime editing can alter DNA directly. On 12 November, it was announced that CRISPR base editors injected directly into people鈥檚 bodies in a small, initial trial had lowered their cholesterol levels.
This approach works because it involves editing liver cells and the liver is the easiest organ to deliver things to due to its blood-cleaning function. However, rapid progress is being made in targeting other organs.
Base editing and prime editing are limited to making tiny changes, though. That is why Tang鈥檚 team and others are creating new gene editors based on so-called jumping genes. Also known as transposons, these are DNA sequences that move from one location on the genome to another. These editors will be able to add or remove large stretches of DNA containing entire genes. Tang thinks this approach will prove superior, pointing out that our genomes have already been extensively modified by transposons.
What has been remarkable about gene editing is the speed at which the technology has advanced since CRISPR鈥檚 inception 鈥� and there is no sign of it slowing.
