CRISPR Infusion Edits Genes Directly in Humans
PhD geneticist and molecular biologist Joel Eissenberg discussing CRISPR results.
— “A watershed moment in modern medicine,” says genetics expert
The promise of gene therapy may finally be realized.
I’ve been a PhD geneticist and molecular biologist for nearly 40 years. During that time, I’ve seen the cloning of many human genes for which inherited diseases were known (e.g., cystic fibrosis, Huntingtons, Duchenne/Becker muscular dystrophy). Each paper reporting the gene cloning concluded with an obligatory paragraph noting that this opened the door to gene therapy.
Sadly, the promised gene therapies have lagged decades behind the discovery and cloning of the affected genes. Instead, most of the progress since cloning has been in diagnostics: we could tell you whether or not you carried a lethal mutation and if so, when and how you would die. Many patients refused to be tested, since nothing could be done anyway.
The rate-limiting step in gene therapy turns out not to be cloning of the gene in question or understanding how and where it is expressed. The challenge has been to deliver the therapy to the proper tissue in therapeutic quantities.
CRISPR/Cas9 genome editing could finally be opening the door to the long-promised genetic therapeutics. There are dozens of clinical trials going on now using this transformative technology to conditions like inherited blindness and sickle cell disease. The latest surprise is that CRISPR genome therapy can be targeted to a solid organ by injection into peripheral blood circulation:
“The NTLA-2001 findings . . . are the “first-ever clinical data suggesting that we can precisely edit target cells within the body to treat genetic disease with a single intravenous infusion of CRISPR,” noted John Leonard, MD, president and CEO of Intellia Therapeutics, which co-sponsored the trial with Regeneron Pharmaceuticals. “Solving the challenge of targeted delivery of CRISPR-Cas9 to the liver, as we have with NTLA-2001, also unlocks the door to treating a wide array of other genetic diseases with our modular platform, and we intend to move quickly to advance and expand our pipeline,” Leonard said in a statement.”
In a First, CRISPR Infusion Edits Genes Directly in Humans, MedPage Today, Judy George
In a First, CRISPR Infusion Edits Genes Directly in Humans, MedPage Today, Judy George
And then there are the industrial apps.
@Ken,
Yes, of course. GMO plants and animals have been around for awhile, and that will only accelerate with CRISPR. There’s also gene drives to control pest species and disease vectors. But those can and have been done with germline modifications which, pace Dr. He’s illicit editing experiments in China, are currently off the table for humans. Delivering somatic cell editing for non-hematopoietic tissues has always been a major barrier, but that may be falling away now. That’s the point of this post.
And beyond?
I can imagine an engineered bacteria that eats plastic; perhaps converts it into something else. Bacteria that are nano manufacturers; …
In medicine; changes the way we look at, treat viruses, doesn’t it?
Ken:
Nano as in Crichton’s “The Prey?”
“Ricky refuses to show Jack the source code for the nanobots, and later Ricky claims that building contractors failed to properly install filters in a certain vent in the building. As a result, hazardous elements such as the assemblers, the bacteria, and the nanobots were blown into the desert, evolving and eventually forming autonomous swarms. These swarms appear to be clouds of solar-powered and self-sufficient nanobots, reproducing and evolving (necroevolution) rapidly. The swarms exhibit predatory behavior, attacking and killing animals in the wild, using code that Jack himself worked on. Most alarmingly, the swarms seem to possess rudimentary intelligence, the ability to quickly learn and to innovate. Jack also learns that Julia helped teach the swarms to improve their intelligence and become more benign, but they regressed when she left. The swarms tend to wander around the plant during the day but quickly leave when strong winds blow or night falls.” Yaken from Wiki
@Ken,
“I can imagine an engineered bacteria that eats plastic; perhaps converts it into something else.”
Bacteria that eat plastic are already known, and research to expand the range of plastics has been going on for years.
https://www.forbes.com/sites/scottcarpenter/2021/03/10/the-race-to-develop-plastic-eating-bacteria/?sh=4a52f3ad7406
the-race-to-develop-plastic-eating-bacteria
As long as it doesn’t mutate into something like “Ice 9” and doesn’t start to eat all plastic or silicone based equipment or something.
@Denis,
Yes. Unforeseen consequences matter. The Forbes link alludes to that.
It’s pretty amazing. One problem with using Cas9/CRISPR to edit genes therapeutically is that Cas9 and CRISPR are proteins and the immune system eats unfamiliar proteins for lunch. The breakthrough was to use mRNA to get liver cells to produce the necessary Cas9/CRISPR proteins on site.
It’s an impressive convergence of technologies.
@Kaleberg,
It is pretty amazing, yes. I was and remain amazed that it works. But not for the reason you mention.
Yes, a challenge for CRISPR/Cas9 is the immune response, but only if there are repeated dosings over weeks. The adaptive immune response is irrelevant for the first dose and if there is only a single dose.
Also, the CRISPR/Cas9 made in the cells is eventually degraded in those cells, and the peptide fragments are displayed on the cell surface and will trigger the adaptive immune system. So again, the key is not the adaptive immune response.
Dr Mengele would have loved to have something like this to work with…
@Rjs,
I wouldn’t know. The Nazis were after a nuclear weapon near the end of the war. Turns out there are dark sides to many technologies.