Recombinetics, a developer in gene-editing technology, has announced its launch of a tripartite transatlantic collaboration called “Target TB.” This new project aims to combat Mycobacterium bovis, the pathogen responsible for bovine tuberculosis. To do this, Recombinetics will work with researchers in Ireland and Northern Ireland and identify the key genes that affect the bovine macrophages’ ability to resist or fight TB infection. The resulting genes could then be changed by editing in vitro embryos.
“If we find valuable genetic variants from the key genes involved in host resilience to TB, we have the opportunity to precision breed those animals, and the subsequent generation should be able to handle the disease better,” explains project leader Dr. Tad Sonstegard of Recombinetics. “In the past, we haven’t been able to identify different genetic variants or knockout genes because we haven’t had the gene-editing technology. The ability to write back to the genome allows us to test different genotypes and see what effect it has on disease phenotypes.”
The long-term project is broken into three basic steps. The researchers working in UC-Dublin (UCD) have been doing disease challenges with M. bovis for some time. “They have a lot of what we call functional genomic data, which allows them to identify the key genes for targeting,” says Sonstegard. “Their job allows them to pick targets based upon their knowledge.”
The next step happens at Queens University Belfast, where the cells to be used for editing are made. “It’s sort of a programmable stem cell,” says Sonstegard. “They would do that from bovine fetal tissue, because these cells are easy to reprogram after editing. Then the Recombinetics lab edits the targets identified by UCD in those special cells that were made in Queens.” Afterward, Recombinetics sends the cells back to Queens University, where they turn them into macrophages in vitro and give those to UCD for TB infection challenge. Finally, the lab in Dublin evaluates the cell phenotype to see whether or not there is an effect from the editing on resilience or resistance to tuberculosis.
This endeavor could be a milestone for bovine health and genetics. Sonstegard notes that to date there are no natural gene variants with major effects on resistance to bovine tuberculosis. “Using the results from UCD studies and a few genome association reports from labs in the United Kingdom and Ireland, we can validate those results and also possibly find new ones through the power of gene editing,” he says.
The pursuit of disease resistance through genetics is a great way to address animal health and welfare, protect public health and help lower cost of production for producers. Because it is a trait linked to health and welfare, it can also help build consumer acceptance to new genetic technologies and innovations.
One of the benefits of gene editing is its ability to introduce sequence variants for new traits into different populations. “If you don’t have certain genetic variants already in your breed or specialized population, even if they’re important for animal welfare and disease resistance, then editing makes an opportunity to introduce without having to crossbreed,” says Sonstegard. “I think for breed registries, that’s important to maintain the integrity of the breed while simultaneously allowing for genetic progress that otherwise would not be possible.” 
Jaclyn Krymowski is a freelance writer based in Ohio.
PHOTO: One of the benefits of gene editing is introducing sequence variants for new traits into different populations. Staff photo.
