Get ready, world, scientists are going to use CRISPR/Cas9 on human patients for the first time, extracting a population of cells, modifying their genomes, amplifying them in tissue culture, and then injecting the modified cells back into the human host. It’s being done in China, where the ethical constraints are a bit more loose, which isn’t always good…but in this case, it sounds like a good, safe (as safe as experimental therapies can be) approach.
They intend to use CRISPR/Cas9 to knock out the PD-1 gene in immune system cells. PD-1 is a cell surface molecule on T-cells that inhibits the cells, and acts as a constraint on immune system activity. The “PD” is short for “Programmed Death”, and what it does is compel the cells to commit suicide when stimulated — so if immune system cells get a bit overzealous and go on a rampage attacking healthy cells, they can be switched off. The immune system has multiple checkpoints to prevent it from going rogue, and this procedure will remove one of them. By knocking out the PD-1 gene, the scientists are creating particularly unrestrained cells that they hope will do a more effective job killing cancer cells, because cancer cells are known to use the signaling mechanisms that tell the immune system to die.
Are there drawbacks and risks? There are always drawbacks and risks. This technique is a variation on an existing pharmaceutical approach, which uses drugs that inhibit PD-1 in cancer patients, so we know a bit about its effects — it’s just that taking out the whole gene with CRISPR/Cas9 is a dramatically thorough way of demolishing the molecule. But we do have some drugs, like Nivolumab and Pembrolizumab, that target PD-1 already and are in clinical trials. We’ve also experimentally knocked out the gene in mice.
So, we have an idea of what could go wrong, and in the immortal words of Dr House, it’s lupus. Or lupus-like effects. By jacking up the immune system and removing one restraint on its activity, you can get complex system-wide problems, which Dr House will tell you are pretty hard to treat, but at least they’re not as severe as terminal cancer. They are also editing a terminal cell type — it’s not going to proliferate — so eventually, we hope after they’ve killed cancer cells, the injected cells will die of natural causes and the effect will fade away.
This is not a treatment that affects the germ cell line, so these patients, if they survive, will not be passing on an edited gene to their offspring. It’s also got to be a rather expensive therapy that has to be customized for each new patient, so it’s not going to be routine. It is a first step into the exciting world of genetically modifying humans, though.