By Christopher Curley
Imagine a custom-engineered virus steering itself into your body to snip and repair damaged DNA and heal a genetic disorder.
Such a procedure might not be the stuff of science fiction for long.
Scientists from Cambridge, Massachusetts, and Dublin, Ireland, have successfully injected the gene-editing tool CRISPR into a live patient in an attempt to treat a rare genetic disease that causes blindness.
The patient was the first in an 18-person clinical trial underway, featuring participants as young as 3 years old.
CRISPR is a sort of “molecular scissors” that allows scientists to cut out and insert custom genetic code into DNA strands.
It has previously been used in therapies to fight cancer and treat sickle cell disease, but in these cases — called “ex vivo” — researchers removed cells from a person’s body, altered them, and then re-inserted them into the patient.
The importance of this procedure
This new “in vivo”(in the body) technique eliminates those extra steps with CRISPR going to work with a set of instructions after being injected into the person, in this case, the patient’s eye.
That’s significant, says Neville Sanjana, PhD, an assistant professor of biology at New York University and a faculty member at the New York Genome Center.
“[In vivo] is an additional layer of complexity in that you have to be able to do the delivery,” he told Healthline. “In the lab, we have many simple ways to tear little holes in cells and get CRISPR in, and then the cells can fix those holes very easily. But when the cells are in situ and in a tissue, it’s much harder to get the CRISPR gene editing reagents in and so you have to use methods like viral vectors repurposed to do therapeutic gene editing.”
Treating the eye, in particular, is a good place to start with this type of in vivo genetic editing, according to Karmen Trzupek, MS, CGC, director of ocular and rare disease genetic services and clinical trial services at InformedDNA, an advisory organization on “the appropriate use and implications of genetic testing.”
“The eye represents a unique opportunity for several reasons,” she told Healthline. “The eye is relatively easy to access, it is a tissue with a high tolerance to viruses, and there is a natural barrier between the retina and the blood that makes it highly unlikely that the inactive virus carrying the CRISPR technology will spread to other parts of the body and create unintended effects.”
Pros and cons
That’s promising, although keep in mind we don’t yet know if this therapy will be successful.
The relative isolation of the eye also means we don’t know how in vivo CRISPR therapies will work in the broader human body.
“Even if this initial CRISPR study proves to be safe, we have a long way to go before proving that it’s safe to administer in many other tissues in the body,” Trzupek said.
But whether in vivo or ex vivo, the pros of gene therapy using technologies like CRISPR probably outweigh the risks — but there are risks.
First, the technology is still new.
“As these gene-editing technologies are still early in clinical development, it’s important first and foremost to make sure they are safe for patients,” said Dr. Bettina Cockroft, chief medical officer at Sangamo a genomic medicine company that helped pioneer the first in vivo gene editing in 2017. “It is also important to make sure we are able to deliver these technologies into cells in an effective way. We will learn more about these technologies as we collect more clinical data and experience.”
“CRISPR is not part of any FDA-approved therapies. It’s not like getting an aspirin or a prescription drug,” he said.
Sanjana added that one thing a person could be concerned about are “off-target effects,” What that means is how often if a doctor is trying to target gene A, do they mistakenly target gene B?
“The primary misconception of CRISPR gene editing is that it is a ‘plug-and-play’ approach that results in the complete correction of a disease gene to a ‘normal’ gene,” Jeffrey Huang, PhD, a research scientist at CHOC Children’s Research Institute told Healthline. “In my experience, CRISPR genome editing in cells and animal models has maximum correction efficiency of 10 to 15 percent. This low efficiency limits the number of inherited disorders that can be treated by current CRISPR editing strategies.”
The good news is that “next-generation strategies currently being developed may dramatically increase the maximum correction efficiency and the therapeutic potential of CRISPR gene editing to treat inherited disorders,” Huang added.
Not ‘The Island of Doctor Moreau’
One thing to keep in mind is that this time of CRISPR gene editing, and all those used in therapies thus far, will not induce changes passed on to offspring.
These gene-editing techniques are known as “somatic” gene editing, which is editing that takes place in a body’s existing cells and cannot be passed down.
That’s contrasted to “germline” gene editing, which is the editing of sperm or egg cells, and the type used to create the “CRISPR twins,” babies born with a genome edited to create HIV resistance.
That incident caused an international uproar and this kind of germline editing is frowned upon by the international community.
“In 2017, the U.S. National Academy of Medicine and the National Academy of Sciences issued a report stating that gene editing should only be used ‘for treating or preventing diseases or disabilities at this time,’” Trzupek said. “The report stressed that gene editing should not be used to alter germline cells.”
What it might mean in the future
It may be early days for CRISPR therapies inside a person’s body, but the reality of this latest advancement points to a promising future.
“In the same way that you know humans see the moon, and they’re like, ‘Wouldn’t it be cool to be there one day?’ — and then you know one day, you actually can be there,” Sanjana said. “I think it’s the same here.”
“For the longest time you know the human understanding is basically been at the time you’re born you essentially win or lose the genetic lottery right or within the first few months,” he added. “Now you’re seeing glimpses of what that future is — a future where all serious genetic disorders might have a specific genetic therapy to treat them.”