Scientists at the Gladstone Institutes (San Francisco) have discovered a way to efficiently edit human DNA, one letter at a time, according to a new study from the biomed research organization published in Nature Methods.
They believe the breakthrough boosts their ability to model human disease and paves the way for therapies that cure diseases by fixing “bugs” in a patient’s genetic code.
“Advances in human genetics have led to the discovery of hundreds of genetic changes linked to disease, but until now we’ve lacked an efficient means of studying them,” explained lead researcher Bruce Conklin, MD.
Conklin said the team’s study addresses the problem of efficiently and accurately capture rare genetic mutations that cause disease and could be the basis for the next phase of human genetics research.
One of the major challenges preventing researchers from efficiently generating and studying these genetic diseases is that they can exist at frequencies as low as 1%, making the task of finding and studying them labor-intensive.
“For our method to work, we needed to find a way to efficiently identify a single mutation among hundreds of normal, healthy cells. So we designed a special fluorescent probe that would distinguish the mutated sequence from the original,” said co-author Yuichiro Miyaoka, of the Gladstone Institutes.
This allowed the researchers to detect mutant cells at a level of sensitivity more than 100 times greater than traditional methods.
The team then applied these new methods to induced pluripotent stem cells, or iPS cells. iPS cells are derived from the skin cells of human patients and have the same genetic makeup (including any potential disease-causing mutations) as the patient. In this case, the research team first used a highly advanced gene-editing technique called TALENs (transcription activator-like effector nucleases) to introduce a specific mutation into the genome.
Scientists hope the breakthrough will help lead to the elimination of genetic-based disorders such as cystic fibrosis and sickle cell anemia.
“Some of the most devastating diseases we face are caused by the tiniest of genetic changes,” said Conklin. “But we are hopeful that our technique, by treating the human genome like lines of computer code, could one day be used to reverse these harmful mutations, and essentially repair the damaged code.”