New Method of Genome Engineering Allowing Scientists to Target and ‘Edit' Faulty Genes

Process could improve treatment of diseases such as hemophilia and cystic fibrosis.

Basil Hubbard, PhD, envisions a world wherein therapeutic treatments for millions of patients are just over the horizon.

With the latest research in genome engineering from Dr. Hubbard, an assistant professor in the Department of Pharmacology at the University of Alberta, this fantasy may be closer to reality than Hubbard originally thought.

In a study published in the journal Nature Methods, a new method that significantly improves the ability of scientists to target specific faulty genes and “edit” them has been developed. This method allows researchers to target and eliminate genetic malfunctions by replacing them 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,” Dr. Hubbard said. “We’re moving towards 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.’ In theory, genome engineering will eventually allow us to permanently cure genetic diseases by editing the specific faulty gene(s).”

Genome engineering involves the targeted, specific modification of an organism’s genetic information. Put simply, much like how a copyeditor edits content for publication, scientists could one day replace a person’s broken or unhealthy genes with healthy ones through the use of sequence-specific DNA binding proteins attached to DNA-editing tools. The field has grown rapidly in the past 20 years and has the potential to revolutionize medical care and treatment options for those with genetic diseases.

While the field does have the potential to change the face of medical history forever, there are still some obstacles that need to be overcome before widespread use in humans is accepted. One of these obstacles, for instance, is how to ensure the proteins only affect the specific targeted genes in need of repair. Currently, the proteins bind to and edit the correct genes the vast majority of the time, but improvements are still needed to ensure off-target genes are not modified in the process. Modifying genes that do not need modification could result in serious health problems for patients.

Dr. Hubbard has a solution to the problem, however, by developing a way to reduce the off-target DNA binding of a class of gene editing proteins known as transcription activator-like effector nucleases (TALENs). This method allows researchers to expedite evolution in proteins autonomously to make them more specific and targeted over time. In other words, the technology allows scientists to say, “I want to target this DNA sequence and I don’t want to target these others,” according to Dr. Hubbard.

Current research in the field of genome engineering involves the treating of monogenic diseases that involve a single gene, as these diseases are much easier to successfully target. Examples of such diseases include hemophilia, sickle cell anemia, muscular dystrophy, and cystic fibrosis.

While the field still has a long way to go with development of genetic engineering technology, Hubbard assures the public that human clinical trials involving sequence-specific DNA-editing agents are already underway. If successful, he suggests the first clinical applications could be seen in the next 10 years.

“We still have to overcome many hurdles but I think this technology definitely has the potential to be transformative in medicine,” Dr. Hubbard said.