Credit: Garrett Ziegler

This year people in the US and Europe are to begin receiving treatment for diseases using the gene-edited tool CRISPR, but has enough work been done to prove it will work effectively?

Although it was first used to edit human cells in a dish back in 2013, writes MIT Technology Review, since then not a lot has actually been done to test it out on humans. But, despite this, it has still been touted as an easy way to alter people’s DNA, promising to eradicate any lethal or lifelong maladies experienced in a treatment. 

In an attempt to finally reinforce its safety and effectiveness, scientists have turned to monkeys. Right now, there isn’t much-published data on CRISPR’s use in monkeys, but early results from small studies point to the prospect of a cure for some diseases, and even to certain challenges. 

Some of the initial experiments involve blood disorders like sickle-cell disease and beta thalassemia. The tool, in particular, could be ideal for both these diseases, scientists think, because each is caused by mutations in a single gene that makes hemoglobin, the protein in the red blood cells that transports oxygen throughout the body. Therefore, both diseases could be simply repaired with a single genetic snip. 

Cynthia Dunbar, a researcher at the National Institute’s of Health is testing this approach in the blood-forming stem cells found in bone marrow. These cells are extracted from monkeys, altered with CRISPR in a lab, and then later infused back into the monkey’s marrow to grow and make new, healthy blood cells. 

In order for the treatment to be effective, a certain percentage of cells need to get edited. Dunbar explained that after three to four months, only about 5% of cells have the necessary edit. To alleviate sickle-cell, “you’d probably need something approaching 20%,” she said. 

Hans-Peter Kiem, from the Fred Hutchinson Cancer Research Center, on the other hand, has been able to extract a certain type of stem cells from monkey’s blood, modify the cells with CRISPR, and put them back into the animals. The editing rate was 40%, and the effects lasted for more than six months. 

“Since monkeys are so similar to humans, I don’t think there’s going to be a huge challenge in translating this work to humans,” Kiem commented. “We use the same technology as we would use in patients.”

He has even squashed any concerns that CRISPR could potentially make accidental cuts to other parts of the genome that aren’t being targeted. Although Kiem hasn’t seen any of these off-target effects in monkeys, his team is sequencing the genomes of the CRISPR-treated monkeys to check.

Biotech CRISPR Therapeutics is also joining the queue, as they use a similar approach in a clinical trial for beta thalassemia that’s slated to begin this year in Europe. The company is also urging regulators to green-light a study on treating sickle-cell disease in people. 

Nevertheless, Editas Medicine is reportedly using monkeys to test its CRISPR-based therapy for a type of inherited blindness. 

The company wants to correct a type of Lebar congenital amaurosis, a rare genetic disorder that causes severe vision loss. Some people suffering from it are born blind or begin to lose their vision when they’re still very young. 

Chief scientist, Charles Albright, says his team has used CRISPR to correct the disease-causing mutation in at least 10% of the light-sensing cells, called photoreceptors, in monkey’s eyes. The treatment is injected directly into the eye. 

Although it wouldn’t bring back a normal sense of sight for patients, Albright explained that it would allow patients to “see reasonably well” and perhaps live more independently. 

“We think we have the potential to restore the ability of photoreceptors to detect light, which is the first step in being able to construct vision,” he said. 

However, there is a slight catch. The monkeys being worked on didn’t have sickle-cell. Instead of looking for signs of improving symptoms, they used a blood test to measure the level of fetal hemoglobin in the animals’ bodies. In addition, the Editas monkeys don’t have vision loss – scientists took tissue from the animals’ retinas and sequenced the DNA to confirm that they’d made the correct edit. 

Researchers could potentially be able to get a better sense of whether a CRISPR therapy in monkeys will translate to cures for people if the animals had the same disease-causing mutations as humans. 

It is here, that gene-editing could play a big part. Jon Hennebold, a researcher at the Oregon National Primate Center, is injecting monkey embryos with CRISPR to breed animals with more genetically precise equivalents of human diseases. 

The end goal is to eventually disable certain segments of DNA to re-create mutations that are known to cause diseases in humans. Those embryos can then be used to artificially inseminate female monkeys, which will give birth to monkeys harboring genetic mutations nearly identical to those in humans. 

Hennebold is attempting to create these “knockout” models for human diseases like hereditary blindness and deafness, among other disorders. Although his lab hasn’t successfully bred such monkeys yet – the researchers have managed to modify embryos and are currently testing them to make sure they’ve made the mutations they want. The next step will be transferring these embryos into female monkeys to generate live offspring that can be used for later studies. 

“Right now, we’re trying to create a storehouse or library of embryos that are relevant for different diseases,” Hennebold explained. 

He went on to warn that scientists must move cautiously into human clinical trials of CRISPR because so little work has been done in monkeys. The question does still remain whether CRISPR will cause immune reactions, and off-target effects also are a concern. 

“We just don’t know enough about what it does outside of the region we want to modify,” he added.