SimpleBio 7

RISPR, an acronym for “clustered regularly interspaced short palindromic repeats,” is a way to edit DNA. With CRISPR, we can change a sequence from ATTGGCG to ATTGGGG or to CCCCCCC, or to anything else. There are other recently developed ways to do this, but they are uniformly unwieldy, time-consuming and inefficient. The joy of CRISPR is that it allows us to edit genes painlessly: It is easily applied and seems to work well in whatever species or cell type we choose.

The history of CRISPR is a prime example of the unexpected benefits of pure research, for it began with a handful of curious scientists not intent on changing the world. In the late 1980s, scientists observed a bizarre section of DNA in some bacteria, consisting of short, identical and repeated “palindromic” sequences that read the same way backward and forward (e.g., CATGTTGTAC). The repeated palindromes were separated by 20-letter segments of unique DNA, segments eventually found to come from viruses that infect bacteria. People soon realized that the CRISPR region was the bacterium’s immune system against dangerous viruses.

CRISPR helps bacteria “remember” previous viral attacks and thus prepares them for future attacks by the same virus. This is analogous to our immune system, which also “remembers” intruders: If you have had measles once, you won’t get it again because the first exposure preps the immune system for subsequent exposures. The way bacteria do this is by storing a segment of the virus’s DNA from the first attack. When the same kind of virus strikes again, the bacterium recognizes that the alien DNA segment has reappeared by matching the stored segment to the intruder DNA. Having identified the intruder as a bad guy, the bacterium can snip up, i.e., destroy, the intruder’s DNA, guided by the same stored-DNA/intruder-DNA match.

Doudna and Charpentier realized that it was possible to subvert the CRISPR system: Instead of viral intruder DNA, we can use the DNA sequence we’re interested in (say, one causing a genetic disease), with the result that CRISPR snips up any and all DNA molecules with the target sequence. Once DNA is snipped up, there are ways to repair it using a different sequence, including a version of the gene that does not produce disease. Presto: gene editing and a path to designer genes.

Rewriting genes has the potential to cure many genetic illnesses. People suffering from sickle-cell disease, for instance, have just a single mutated “letter” in the DNA coding for their hemoglobin . It shouldn’t be hard for CRISPR to replace that letter in embryos or bone marrow, curing the millions who suffer from this devastating malady.