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.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.
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.
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.”