There are some concerns surrounding the CRISPR gene-editing tool, but a recent study involving this tool showed positive results at helping patients with a rare eye disorder.
Gene editing is a frontier sector of healthcare research and has the potential to tackle various diseases – with a recent study showing its potential for restoring vision.
The study involved CRISPR, a gene-editing tool that has been a source of wonder and controversy for years now. Supporters of the tool say it holds great promise to eradicate various horrific conditions such as Huntington’s disease, or spot the right targets to treat lung cancer.
But there are concerns surrounding this tool, as one study showed that CRISPR can potentially cause irreparable damage to cells and unforeseen mutations.
Despite the concerns, researchers are continuing to find promising results when using this gene-editing tool. A recent study showed positive results when it comes to using CRISPR to treat genetic eye diseases.
Prof Mark Pennesi was one of the researchers involved in this study. He is a director of ophthalmic genetics at the Retina Foundation and a professor of ophthalmology at the Oregon Health and Science University.
Speaking to SiliconRepublic.com during the Retina International World Congress in Dublin, Pennesi said the study focused on 14 individuals with a form of leber congenital amaurosis – a severe genetic eye disease that has serious impacts on vision.
“These patients are born with severe vision loss,” Pennesi said. “Most are legally blind, even at a young age, and will lose vision over the course of their lifetime, some going completely blind.”
The study showed positive results in more than half of those involved in the study, including the two children that were involved. It is hoped that the results of this study will pave the way for future research and help more children with similar genetic eye diseases.
How CRISPR works
Pennesi said this form of leber congenital amaurosis is caused by mutations in a gene called CEP290 and that if someone has two mutations in this particular gene, they’ll have this disease.
For certain genetic eye diseases, there is the option to tackle the issue through genetic replacement therapy – using products such as Luxerna. But Pennesi said this particular gene is too large to be viable for genetic replacement, which is why the team used CRISPR.
Pennesi said the CRISPR-Cas tools they used are “essentially bacterial proteins that can cut DNA” and were originally used “for bacteria to protect themselves against viruses”. The CRISPR tool alters these proteins so they can cut human DNA.
“The trial was sponsored by a company called Editas and they designed a vector that’s essentially the shell of a virus,” he said. “Inside of that are different components, including a Cas protein, which can cut DNA, and then two guide RNAs which act as homing beacons to bring that Cas protein to where the mutation is.”
This mutation acts as a “stop signal” in the patients that prevents a certain protein from being made – the cause of the vision loss. The Cas protein is designed to cut that mutation to allow the protein to function normally.
“Interestingly, even though these patients have very severe vision loss, there are still photoreceptors present in their retina, they’re just not working,” Pennesi said.
“When you restore the protein function, you actually can get an improvement in vision. And so, we did see that in a number of the patients where they had improvement in their sensitivity to light, some had improvement in their visual acuity, some had improvement in their ability to navigate a mobility test, and many of them reported subjective improvements in just their daily tasks of living.”
The CRISPR-Cas protein was inserted into the eyes of patients by taking out some of the gel of the eye and using a very fine needle – about the size of a hair – to inject the virus shells into the eye.
Plans for the future?
Pennesi spoke very positively about the results of the study, particularly in the fact that both of the children in the study reported an improvement in their vision thanks to CRISPR.
That’s very exciting, because it’s certainly possible that the younger we treat, we might be able to get better results,” he said. “But even some of the older patients showed improvement as well, meaning that it may not be too late for many patients. In fact, I think one of our best patients was 59.
“I think we’re going to utilise this technology going forward for other genes.”
In regards to the concerns around CRISPR and its potential to impact other genes, Pennesi said there was a positive element to the fact it was being injected into the eye – as it is not being introduced throughout the whole body.
“It’s not going to go to the reproductive system,” he said. “So this is not something that would get passed on. Furthermore, we can engineer the vectors to be specific to targeting a certain type of cell, we can control the expression of the protein such that they’re only in a certain type of cell.
“But we have to always be cognisant of the possibility that there could be off-target effects. And this is a reason that we’re going to need to monitor these patients, probably for the rest of their lives, to make sure there are no adverse effects. But I think the way that we’re doing it here, we’ve been very cautious and put a lot of kind of protective mechanisms in.”
Pennesi spoke positively about CRISPR for treating eye diseases, but he doesn’t believe it’s a one-size-fits-all solution, as there are hundreds of different genes connected to eye diseases and it could be difficult to create hundreds of different gene therapies.
“I think that at the end of the day, curing these diseases, it’s not going to be just one treatment, it’ll likely be a combination,” Pennesi said. “Just like when you treat cancer, you rarely give one drug, it’s usually a combination of several drugs so that you can get a synergistic effect. “So we’re exploring all the different avenues.”
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