New research from the University of Texas at Austin dramatically expands the number of natural versions of a previously under-explored system of genetic alteration, giving researchers a host of potential new tools for large-scale gene editing.
This development, which was awarded a Nobel Prize in 2020, opens the way for any genetic change to be made in any organism.
New resources to work on genetic modifications
Previously, other scientists had already identified groups of genes that use CRISPR, the modification system identified in this study, to insert themselves at different places in an organism’s genome. Previous work has shown that they can be used to add an entire gene or large DNA sequence to the genome, at least for bacteria.
Now, a team led by Ilya Finkelstein and Claus Wilke at UT Austin has expanded the number of probable gene clusters, called CAST, from about a dozen to nearly 1,500. “With CASTs, we could potentially insert many genes, called ‘gene cassettes’, that encode multiple complicated functions”, he pointed to his home of studies Finkelstein, associate professor of molecular biosciences, who conceived and directed the research. Among other things, this opens the possibility of treating complex diseases associated with more than one gene.
Using a supercomputer, the team sifted through the world’s largest database of microbe genome fragments that have not yet been cultured in the lab or fully sequenced. The researchers estimate that if the search had been run on a powerful desktop computer, it would have taken years. Instead, with one of the university’s supercomputers, the final analysis was completed in a few weeks.
“The term for this is bioprospecting.”said Finkelstein. “It was like sifting through a large amount of silt and trash to find the occasional gold nugget.”
The UT Austin team found 1,476 new putative CASTs, including three new families, doubling the number of known families. They have already experimentally verified several of these and plan to continue testing more. Ultimately, Finkelstein predicts that most will turn out to be true CAST.
«If you have only a handful [de CAST], it is unlikely that you have the best that exist »Wilke said. “By having more than a thousand, we can begin to discover which ones are easier to work with or more efficient or accurate. Hopefully there are new gene-editing systems that can do things better than the systems we had beforehand. “added.
In the short term, Finkelstein said that many of these new systems should be adaptable to genetically engineered bacteria. The long-term challenge, Finkelstein said, is “taming” the systems to work in our cells. “The holy grail is to make this work in mammalian cells”, dijo Finkelstein.
The researchers published their results in the journal Proceedings of the National Academy of Sciences.