Tuesday, November 17, 2015

CRISPR and the Editing of Human Genes

After decades of people wondering what it will mean, the editing of human genes is here. A biotech startup called Editas plans to start testing soon on a genetic fix for a rare form of blindness, using the technology known as CRISPR. The next paragraph is a somewhat technical description of what CRISPR is, should you be curious; if you don't care and just want to read about its use in humans, skip that paragraph and go on.

CRISPR stands for clustered, regularly interspaced, short palindromic repeat, which describes short sections of bacterial DNA that seem to have been copied from viruses. They serve to mark off special sections of the bacterium's DNA. When a virus attacks, the bacterium can insert a key gene from the virus into the space marked off by the CRISPRs and then make many RNA copies of the gene, which guide the bacterium's immune system to target the invader. Bacteria have a whole class of proteins designated Cas, for CRISPR-associated, which are involved in this gene splicing and copying exercise. Studying these unusual gene systems, biologists realized that Cas proteins can easily be instructed via "guide RNA" to snip DNA at any chosen point. Thus, if you know that a particular section of DNA is damaged, you can create RNA that matches it and instruct a protein like Cas9 to snip out the damaged section and replace it with an unbroken version. Biologists have been able to snip out problem DNA segments for 15 years now, but CRISPR is both more precise than older systems and much, much cheaper, and by cheap I mean that you can get a batch of guide RNA made to order for only $30. Suddenly, precise gene editing is within reach of any lab and any hospital.

CRISPR is only three years old but it is already revolutionizing genetics. One of the obvious uses is to replace damaged DNA sections that cause genetic diseases, and that is what Editas plans to do:
Editas, which had not previously given a timeline for an initial human test of CRISPR, will try to treat one form of a rare eye disease called Leber congenital amaurosis, which affects the light-receiving cells of the retina.

The condition Editas is targeting affects only about 600 people in the U.S., says Jean Bennet, director of advanced retinal and ocular therapeutics at the University of Pennsylvania’s medical school. “The target that they have selected is fantastic; it has all the right characteristics in terms of making a correction easily,” says Bennett, who isn’t involved in the Editas study.

Children with LCA are born seeing only large, bright shapes, and infants are diagnosed when they don’t look into their mother’s eyes or react to colorful balloons. Their poor vision can progress to “stone cold blindness where everything is black,” says Bennett.

Editas picked the disease in part because it is relatively easy to address with CRISPR, Editas CEO Katrine Bosley said. The exact gene error is known, and the eye is easy to reach with genetic treatments. “It feels fast, but we are going at the pace science allows,” she said. There are still questions about how well gene-editing will work in the retina and whether side effects could be caused by unintentional changes to DNA.

Editas plans to deliver the CRISPR technology as a gene therapy. The treatment will involve injecting into the retina a soup of viruses loaded with the DNA instructions needed to manufacture the components of CRISPR, including a protein that can cut a gene at a precise location. Bosley said in order to treat LCA, the company intends to delete about 1,000 DNA letters from a gene called CEP290 in a patient’s photoreceptor cells.

After the edit, preliminary lab experiments show, the gene should function correctly again. Bosley said Editas still needs to test the approach further in the lab and in animals before a human study starts.
I think this is fabulous. Of course, once this technology is refined and made commercially available, it could be used to edit any gene. But I don't find that as scary as some other people do; as I have written here before, all important human characteristics -- height, intelligence, skin color, etc. -- are the result of dozens or hundreds of genes working together. So we are nowhere near a world in which parents edit their fertilized ova to create a blonde, athletic genius.

And we still have to make this work, as wikipedia explains:
In April 2015, scientists from China published a paper in the journal Protein & Cell reporting results of an attempt to alter the DNA of non-viable human embryos using CRISPR to correct a mutation that causes beta thalassemia, a lethal heritable disorder. According to the paper's lead author, the study had previously been rejected by both Nature and Science in part because of ethical concerns; the journals did not comment to reporters. The experiments resulted in changing only some of the genes, and had off-target effects on other genes; the scientists who conducted the research noted that CRISPR is not ready for clinical application in reproductive medicine, and said to a reporter at Nature: “If you want to do it in normal embryos, you need to be close to 100%.... That’s why we stopped. We still think it’s too immature.”

1 comment:

  1. "I think this is fabulous. Of course, once this technology is refined and made commercially available, it could be used to edit any gene. But I don't find that as scary as some other people do; as I have written here before, all important human characteristics -- height, intelligence, skin color, etc. -- are the result of dozens or hundreds of genes working together. So we are nowhere near a world in which parents edit their fertilized ova to create a blonde, athletic genius."

    With a single custom order edit apparently running at $30 dollars, what's to stop people from simply placing dozens or hundreds of orders if they have the money? You could make 500 changes to your child's genetics for $15,000 and added fees. Instead of a luxury car, people would buy luxury genes.

    Seemingly the only thing stopping us at this point is incomplete knowledge of the functions and interplay of all our genes. But will that still be an obstacle in 100 or even just 50 years?

    Eugenics has long been something of a moot discussion because it's just so darn hard to pull off without resorting to acts everyone agrees are abominable. But if it gets to the point where you can buy a "suite" of genetic modifications for the price of a new economy car, it's suddenly going to become a very heated debate.

    There's also the concern of this sort of technology being used maliciously. How tempted might the government be to issue genetic markers to convicted criminals for future identification? Not just discreet ID tags that require gene samples to read, but active phenotypical changes, such as causing visible pigmentation changes on the face or hands to facilitate visual identification? Or what about forced sterility for undesireables, undertaken at a nearly invisible genetic level?

    There is definitely cause for concern and caution. The problem is that the technology itself is probably far less dangerous than the people who would want to use it are.

    ReplyDelete