While Rose spent her short life helping break the stigma attached to a devastating disease, geneticist David Liu dedicated his career to developing ways to alter the genetic code that claimed his life at such a young age.
“That a single misspelling in her DNA ended Adalia’s life so soon is a loss to all of us,” said Liu, professor of chemistry and chemical biology and director of the Merkin Institute of Transformative Technologies. in Healthcare at Harvard University.
“I didn’t have the chance to meet Adelia before she passed away in January. But every progeria patient I’ve met has been warm, charming, articulate and deeply inspiring,” Liu told CNN.
Liu hopes the tool will soon be used in human clinical trials to reverse progeria in humans.
“The base editor goes into the cells of the animal, finds the error that in progeria is a C to a T, and changes the T back to C,” Liu told an audience Tuesday at the conference. Life Itself, a conference on health and health. wellness event presented in partnership with CNN.
“And that’s it. We never go back to the patient – it’s a one-time treatment that permanently corrects the mutation that causes the disease,” said Liu, who is also vice president of faculty at the Broad Institute. from MIT and Harvard. , a biomedical and genomics research center in Cambridge, Massachusetts.
“The era of human therapeutic gene editing is not just coming. It’s already here,” Liu told the Life Itself audience.
The advantage of a “nick”
Scientists modify genes using enzymes that have been designed to target a specific DNA sequence, cut out the offending genetic material and insert replacement DNA. For decades, however, known methods of modifying our genetic code have been clumsy, often missing their mark or cutting off too much or too little genetic material.
However, like older editing technologies, CRISPR-Cas-9 cuts both DNA strands, which has some drawbacks, Liu said. For one thing, some cells rolled back edits after they were made, he said, “so the overall editing efficiency was very low.”
Liu’s team found that if you cut just one strand of the DNA double helix with CRISPR-based technology and “cut” the other, the cell was more likely to implement the corresponding change. on the second strand without complaining – and with fewer mistakes.
Editing larger DNA sequences
Liu and his team also invented another type of CRISPR-based tool called a master editor, which could make larger and more complex edits to DNA than basic editors could not.
“An analogy I like to use is that the original CRISPR-Cas_9 is like scissors that cut DNA. Core editors are like pencils that precisely correct letters by changing them to one of four different letters” , explained Liu. “And master editors are like molecular word processors that do true search and replace of larger sequences.”
Only a third of the 75,000 known “spelling mistakes” that cause genetic diseases can be corrected by grassroots editors, Liu said. “But add our main editor, and in between, they can finally free us from the vast majority of misspellings in our DNA,” he told the Life Itself audience.
“We have to make sure that all of these different technologies go through clinical trials very carefully,” Liu added. “But if they prove to be safe and effective, then one could imagine treating not just the rare misspellings that cause serious genetic diseases, but perhaps even treating genetic variants that we know contribute to many terrible diseases like Alzheimer’s disease or hypercholesterolemia.”
However, Collins added, “It’s unclear whether master editing can insert or delete DNA the size of complete genes – which can contain up to 2.4 million letters.”
Gene editing will not be a solution for all of life’s diseases, Liu warned. For example, infections and cancer cells are two areas that are not well suited for gene editing, as you would have to touch every cell to stop the disease.
“But with many genetic diseases, we often only need to modify 20% or 30% of the tissues to save the genetic disease,” Liu said. “That’s what we’ve seen with progeria and sickle cell disease in mice. A little editing can go a long way to saving these diseases in animals, and we’re thinking about humans too.”