Innovation

New Gene Editing Method Paves Way For Curing Monogenic Disease, Like Cystic Fibrosis And Muscular Dystrophy

DNA
A new method of genome engineering allows scientists to more accurately pinpoint the faulty genes that cause diseases and “edit” them, replacing the damaged genetic code with healthy DNA. Dan Century CC BY 2.0

In a perfect world, we’re all living long, healthy, prosperous lives without ever stepping into a doctor’s office or a hospital emergency room. We’re growing old without having to worry about creaky joints, random aches and pains, or the myriad illnesses that can develop. Unfortunately, this perfectly healthy life is a speck on the horizon, if it’s even there at all. But with genome engineering, we may be one step closer to getting there.

Basil Hubbard, an assistant professor of pharmacology at the University of Alberta's Faculty of Medicine & Dentistry, has a dream of a world where millions of patients who suffer from debilitating diseases, like muscular dystrophy and cystic fibrosis, can be treated with the science of genome engineering. His research, published in Nature Methods, shows off a new technology that allows scientists to more accurately pinpoint the faulty genes that cause diseases and “edit” them, replacing the damaged genetic code with healthy DNA.

"There is a trend in the scientific community to develop therapeutics in a more rational fashion, rather than just relying on traditional chemical screens," Hubbard said in a press release. "We're moving toward a very logical type of treatment for genetic diseases, where we can actually say, 'Your disease is caused by a mutation in gene X, and we're going to correct this mutation to treat it.'"

He says that, in the future, genome engineering will let us "permanently cure genetic diseases by editing the specific faulty gene(s)." People who are suffering from a disease that they know will be passed down to their offspring can take some solace in the fact that someday — soon, hopefully — their children or children’s children won’t have to go through the pain and suffering they’re going through.

Genome engineering is the modification of an organism’s genetic information. Similar to how a software web developer rewrites code, a scientist would go into a person’s DNA, “fix” the broken or unhealthy genes, and replace them with healthy genes using sequence-specific DNA binding proteins attached to DNA-editing tools. This ability to edit genetic code is a little ways off, as current technologies struggle with getting proteins to bind, making them unable to edit the correct genes. Researchers also need to improve the technology so that it will ensure other genes aren’t modified — an effect that could have serious health consequences.

Through his research, Hubbard devised a way to reduce off-target DNA binding of a class of gene editing proteins known as transcription activator-like effector nucleases (TALENs). This allows scientists to evolve the proteins freely, which in turn makes them more specific and targeted over time. "This technology allows you to systematically say, 'I want to target this DNA sequence, and I don't want to target these others,' and it basically evolves a protein to do just that," Hubbard said. "Using this system, we can produce gene editing tools that are 100 times more specific for their target sequence."

The research in genome engineering is primarily focused on monogenic diseases, which involve a single gene, because they’re much easier for scientists to handle at the moment. These diseases include hemophilia, sickle cell anemia, muscular dystrophy, and cystic fibrosis.

Human clinical trials using this method are already underway, with the expectation that it’ll be used widely within the next decade, Hubbard said.

Source: Hubbard BP, Ahmed H Badran, John A Zuris, et al. Continuous directed evolution of DNA-binding proteins to improve TALEN specificity. Nature Methods. 2015.

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