CRISPR Marches Forward: Correcting a Disease in Animals

As we previously discussed, CRISPR-mania is sweeping the globe. (Okay, it might not be as big as Beatlemania, but more than a few life science researchers have probably squealed in delight.) The CRISPR system, derived from bacteria’s fight against viruses and tailored so that it can snip away genetic material in other organisms, has generated considerable excitement for its potential use as a type of molecular surgeon, cutting away harmful genes that lead to human disease. Companies in the know about CRISPR are providing their services through Scientist.

Now, scientists have used methodology based on CRISPR to target a genetic disease.¹ They were interested in a rare human condition known as hereditary tyrosinemia type I (HTI), in which the body cannot completely break down the amino acid tyrosine, leading to severe liver damage that proves fatal. Lab mice are available that harbor the same genetic mutation which is harmful to mice and men alike. Treatments are available for human HTI, so pursuing the disease in mice through a CRISPR system was presented as a proof-of-principle. The researchers administered a DNA-chopping protein that is associated with CRISPR (Cas9), as well as a “guide” RNA to lead the protein to the right place in the mouse genome. They also introduced a stretch of non-defective DNA. That way, when the mice DNA is broken by Cas9, the natural repair system is able to sew in the correct sequence. Mice receiving one type of CRISPR package did not experience the swift weight loss observed with this disorder. Their livers had extensive patches of healthy cells, and markers of liver damage were greatly reduced, compared with controls.

Interestingly, a correction rate of only about 1/250 cells was determined, but liver cells with the healthy gene can repopulate the organ.² No off-target effects were found. Studying the transcription of the gene showed that, indeed, the modified RNA was transcribed. Some developments are needed before an approach like this could be available for humans. For one, the CRISPR treatment was delivered to the liver by hydrodynamic injection, a rapid administration of the material in a large volume of solution. This fast and furious injection would be dangerous for human patients, and a suitable alternative would need to be discovered. What’s more, many diseases may not be cured if only 1/250 cells are positively affected. However, these challenges have not dampened researchers’ excitement, where the hope that one day, CRISPR-based systems will be a solution to the tricky problem of mending troubled genes.