Liver Disorder in Adult Mice Repaired Via Gene Editing

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Inserting foreign DNA into the genome before the organism is born is fairly easy, but making changes further along in embryonic development gets difficult, due to the number of cells that need to be altered. Of course, adding DNA is much easier than actually editing an existing gene. However, a team of geneticists led by Daniel Anderson from MIT have successfully managed to edit the genes of living adult mice, reversing a rare liver disorder. The results of the study were published in the journal Nature Biotechnology.

Tyrosinemia is a rare, potentially fatal genetic disorder which affects how the liver is able to break down excess amounts of the amino acid tyrosine, due to a single mutated base pair in the gene that encodes the enzyme fumarylacetoacetate hydrolase (Fah). This mutation is recessive, which requires both parents to have the mutation in order for it to be passed down to the offspring. 

The gene editing is accomplished with using clustered regularly interspaced short palindromic repeats (CRISPRs), which are very characteristic of DNA in viruses. Certain bacteria have a defense system that allows them to target and snip the threatening viral DNA in the CRISPR-associated (Cas) genes. This CRISPR-Cas system has been exploited so that the bacteria can snip out a specific mutation and replace it with a predetermined replacement.

In this study, the programmed cells were injected into the mice, where they corrected the Fah mutation, which in turn established a functional tyrosine catabolism pathway. Though the treatment only took in about 1 out of every 250 hepatic cells initially, eventually the livers began to take on the wild type phenotype and functionally eliminated the type I tyrosinemia. The fact that such gene editing was actually accomplished in a living adult animal is a huge step forward. 

In January, a research group out of China successfully edited the genomes of two monkeys at the single cell embryonic stage using the same CRISPR-cas system. The success marked the first time that gene editing had been successful in a primate. While it is easier to edit the genome at the single cell stage than as an adult, it does give encouragement that this technique could be useful for humans.

It goes without saying that the implications of this study could be huge. Type I tyrosinemia is rare and occurs in about 1 in 100,000 human births, but as research continues, a wider range of genetic mutations could be targeted and the CRISPR-cas system could potentially target more than one single base. This could allow doctors to eliminate a genetic predisposition to diseases like Alzheimer’s, Huntington’s, and even various types of cancer. The researchers are currently keeping quiet on the disease they’ll attempt to treat next, but have mentioned it will be serious illnesses which do not have any current method of treatment.

Of course, there is the potential for this treatment to cause extensive damage, if the CRISPR-cas system cuts into the wrong place. The researchers are currently working on finding the best way to deliver the treatment as well as generating a synthetic alternative to the bacteria, for safety and efficacy purposes.

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