While Rose spent her short life helping to break down the stigma attached to a devastating illness, geneticist David Liu has devoted his career to developing ways to alter the genetic code that governed her life at such a tender age has cost.
“That a single misspelling in her DNA ended Adalia’s life so early is a loss for 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 a chance to meet Adelia before she passed away in January. But every Progeria patient I’ve met has been warm, charming, articulate and deeply inspirational,” 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, looks for the error that is a C into a T in progeria, and turns the T back into a C,” Liu said ahead of his presentation on the topic at the Life Itself conference, a health and wellness event presented in partnership with CNN.
“And that’s it. We never get back into the patient — it’s a one-time treatment that permanently fixes the mutation that causes the disease,” said Liu, who is also vice faculty chair at MIT and Harvard’s Broad Institute, a biomedical and genomics professor Research Center in Cambridge, Massachusetts.
“The age of human therapeutic gene editing is not yet to come. It’s already here,” Liu said.
The benefit of a “nick”
Scientists edit genes using enzymes engineered to target a specific sequence in DNA, cutting out the offending genetic material and inserting replacement DNA. For decades, however, known methods of altering our genetic code were clumsy, often missing the mark, or cutting off too much or too little genetic material.
However, like older editing technologies, CRISPR-Cas-9 cuts both strands of DNA, which has some downsides, Liu said. For one, some cells reverted the changes after they were made, he said, “so the overall efficiency of editing was very low.”
Liu’s team discovered that if you cut just one strand of the DNA double helix using CRISPR-based technology and “nodded” the other, the cell was more likely to make the corresponding change to the second strand without complaint — and with fewer errors.
Editing larger DNA sequences
Liu and his team also invented another type of CRISPR-based tool called the Prime Editor that could do larger, more complex edits to DNA than basic editors couldn’t.
“One analogy I like to use is that the original CRISPR-Cas_9 is like scissors cutting DNA. Basic editors are like pencils that precisely correct letters by changing them to one of four different letters,” Liu explained. “And prime editors are like molecular word processors that do real search and replace on larger sequences.”
Only a third of the 75,000 known “spelling errors” that cause genetic diseases can be corrected by the base’s editors, Liu said. “But add our chief editor, and the two of them can finally free us from being bound to the vast majority of misspellings in our DNA,” he said.
“We have to make sure that all these different technologies go through clinical trials very carefully,” Liu added. “But if they prove safe and effective, one could envision not only treating rare misspellings that cause serious genetic diseases, but perhaps even treating gene variants that we know cause terrible diseases like Alzheimer’s.” disease or high cholesterol.”
But Collins added, “It’s unclear whether prime editing can insert or remove DNA the size of full-length genes — which can contain up to 2.4 million letters.”
Genetic editing will not be a solution to all of life’s diseases, Liu warned. For example, infections and cancer cells are two areas that are not well suited for gene editing, since you would have to touch every cell to stop the disease.
“But for many genetic diseases, we often only have to edit 20% or 30% of the tissue to save the genetic disease,” Liu said. “We’ve seen that in progeria and sickle cell anemia in mice. A little bit of editing can go a long way in saving these diseases in animals, and we think in humans, too.”
Correction: A previous version of this story incorrectly attributed comments made by Liu during the Life Itself conference. They came from an interview.