Gene editing opens the door to a world without genetic disorders


Two unrelated studies published in the journal Nature Medicine highlight the progress that’s been made in one of the major goals of gene editing: preventing the perpetuation of geneticdisorders.

Both studies build on existing  knowledge of the CRISPR-Cas9 complex, a genome editing tool that has gained a lot of popularity in recent years and has since been at the forefront of the discussion on gene editing. The CRISPR-Cas9 system utilizes highly specific DNA editing techniques taken from prokaryotic cells and originally used to fight off viruses. Harnessing the power of this system, scientists can entirely cut out discrete sets of genes.

The first study reported was conducted by researchers at the University of Pennsylvania whose aim was to rid rats of a rare liver disease — hereditary tyrosinemia type 1 or HT1 — involving the inability to break down a specific amino acid, tyrosine. This inability causes liver and kidney dysfunction and intellectual disabilities.

The usual treatment for this disease is a strict diet and a drug called nitisinone that treats some of the effects.

If the disease is left to progress, it could result in liver failure or cancer. Since HT1 is essentially the result of a harmful mutation, the researchers wanted to see if they could fight the mutation as a whole by deleting the sequence responsible for the dysfunction.

They went on to report that the mice treated with gene editing exhibited greater liver function than those who received nitisinone. Though this study did not use the CRISPR-Cas9 complex by itself, the point of the study was to use another system, base editor 3, in order to circumvent an issue that is often touted against the functionality of the CRISPR-Cas9 system.

The complaint often lobbied against the CRISPR-Cas9 system is that after the DNA has been cut, the subsequent reparation process can produce unintended consequences, thereby causing more problems than the unit started off with. The fact that the mice treated with base editor 3 remained stable months after they were born pointed to the idea that gene editing does not necessarily have to be a volatile process.

“We think this represents a safer and more precise way to make changes in the genome,” said Dr. Kiran Musunuru of the Perelman School of Medicine at the University of Pennsylvania and a co-leader of the study, in an interview with Business Insider. “It’s is [sic] the better way forward if you want to take CRISPR into the clinic.”

The second study from the journal involved researchers at the science, technology, engineering and mathematics university, ETH Zurich in Switzerland, who were working with mice and a metabolic liver disease, phenylketonuria, or PKU, which is similar to HT1 in that the treatment is the same — a specialized diet — and both diseases are caused by genetic abnormalities.

In an organism with PKU, the body can no longer metabolize the amino acid phenylalanine, letting its count build up and end up disrupting the neural functions of the organism.

Similar results seen in the first study were found in the second, corroborating the story proposed by the University of Pennsylvania of the positive effects of CRISPR usage with base editor 3 guidance. Both teams of scientists involved in the research came to their own conclusions that though this is a step in the right direction, more work needs to be done before this can be attempted on humans. Specifically, the Switzerland researchers intend to study larger animal models, such as the pig, which would be more closely related to human than mice are.

“A lot more animal work needs to be done before we can even think about applying this [fetal genome editing] clinically,” said William H.Peranteau, a pediatric and fetal surgeon at the Children’s Hospital of Pennsylvania, in science news-site, STAT.

“But I think fetal genome editing may be where fetal surgery [which is now routine] once was, and that one day we’ll use it to treat diseases that cause significant morbidity and mortality.”

Due to this revelation that we may possibly be able to halt certain genetic disorders, there comes hope that one day there will be no true genetic disorders and that long and healthy lives can be all but guaranteed at birth.