Details of the CRISPR-Cas9 system and its ability to introduce precise and apparently permanent changes to the genetic code were first published in 2013. Developed from a bacterial system that confers anti-viral protection, the ingenious CRISPR system uses the DNA-cleaving Cas9 enzyme bound to an RNA guide that directs it to the site of interest in the genome and a DNA template strand to direct cellular DNA repair – effectively removing a specific DNA section and replacing it with another.
Last month the first exemplar of therapeutic application of genome editing using the CRISPR system in a mouse was published in Nature Biotechnology. Adult mice with the murine form of hereditary tyrosinemia type I (HTI), a rare and severe genetic metabolic disease caused by mutation of the gene that encodes the enzyme fumarylacetoacetate hydrolase (FAH) were treated with a CRISPR construct including the healthy gene sequence, administered via high-pressure injections.
The gene sequence was corrected in about 1 in every 250 hepatocytes (liver cells), which subsequently proliferated until they comprised around a third of the total hepatocytes and provided an effective cure. Normally HTI prevents the metabolism of the amino acid tyrosine, which accumulates and can cause liver failure; it can be treated with a drug that blocks tyrosine production and a special diet. However, the mice who received genome editing survived in the absence of this previously essential drug treatment.
These results are an important step towards the goal of successful, long-term gene therapy to treat serious genetic diseases in humans, and underline the potential of the CRISPR-Cas9 system as a tool for genome editing.
The new patent includes description of how the system could be used to treat specific genetic diseases, including many that lack effective treatments. Researchers in many different laboratories are already enthusiastically using and customising it, and will be hoping the patent will not prove a barrier. Encouragingly, Broad Institute director Eric Lander said: “Consistent with the Broad’s mission to accelerate the understanding and treatment of disease, we are committed to empowering the global research community by making this technology broadly available to scientists for research around the world”. This suggests that licensing arrangements for the technology should not be prohibitively expensive or in other ways likely to limit widespread application.