Washington: A new technique that allows for efficient editing of the human genome one letter at a time may help scientists identify and cure rare genetic mutations that cause disease.
Scientists at the Gladstone Institutes in US say they have solved one of science and medicine’s most pressing problems: how to accurately capture rare genetic mutations that cause disease – as well as how to fix them
“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,” said Gladstone Investigator Bruce Conklin.
“To meet this challenge, we must have the capability to engineer the human genome, one letter at a time, with tools that are efficient, robust and accurate. And the method that we outline in our study does just that,” Conklin said.
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 per cent, making the task of finding and studying them labour-intensive.
“For our method to work, we needed to find a way to efficiently identify a single mutation among hundreds of normal, healthy cells,” said Gladstone Research Scientist Yuichiro Miyaoka, the paper’s lead author.
“So we designed a special fluorescent probe that would distinguish the mutated sequence from the original sequences.
“We were then able to sort through both sets of sequences and detect mutant cells – even when they made up as little one in every thousand cells. This is a level of sensitivity more than one hundred times greater than traditional methods,” Miyaoka said.
The team then applied these new methods to induced pluripotent stem cells, or iPS cells. These cells, derived from the skin cells of human patients, 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 to introduce a specific mutation into the genome.
Some gene-editing techniques, while effective at modifying the genetic code, involve the use of genetic markers that then leave a ‘scar’ on the newly edited genome.
These scars can then affect subsequent generations of cells, complicating future analysis.
Although TALENs, and other similarly advanced tools, are able to make a clean, scarless single letter edits, these edits are very rare, so that new technique from the Conklin lab is needed, researchers said.
“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,” Conklin said.