A new gene editing technique discovered by UO researchers significantly reduces the time spent on research, making it possible to explore several areas that were previously unavailable. Thanks to this method, biologists can now compare many versions of a gene to find mutations that give rise to specific traits, while also tracking their evolution over time.
By conducting this type of research, scientists have taken an important step towards identifying mutations relevant to human health or understanding the mechanisms underlying human diseases. Although mass gene editing techniques have been developed before for single-celled organisms such as bacteria and yeast, this is the first time they have been possible on this scale in an animal.
Gene editing takes a leap forward
“In biology, we spend a lot of time working with genetic mutants. But in animals we are limited by how many genetic mutants we can produce at one time,” says the researcher Zach Stevenson, who helped design the technique. “This is a new way to get around that bottleneck.”
Stevenson and his colleagues describe their new technique in a preprint published on bioRxiv. I link it to you here.
The system, developed with the tiny worm C. elegans, it could also work in other laboratory animals, such as flies or mice, says Stevenson.
Because it is important
There are many reasons why scientists may want the ability to create many genetic mutations at the same time. For example, they might be editing for a mutation that makes an animal resistant to a specific drug, or able to survive under certain conditions, or less susceptible to a disease.
They may need to look at dozens or even hundreds of possible variations on a gene to find the most effective one.
The engineering of this type of editing experimental genetic it is extremely slow in animals. Each mutant strain, a collection of worms with a predetermined genetic modification, must be created one by one. “Usually,” Stevenson says, “it takes seven to 10 hours of practice” to create a single mutant. This newly discovered system allows you to “create tens of thousands” in the time it now takes to create just three or four.
How the new method works
To speed things up, Stevenson and his colleagues designed a way to compress hundreds or even thousands of possible mutations into a single “library.” Every book in the library is a small fragment of genetic code, in itself insignificant and non-functional. Each fragment fits into an engineered “niche” in the gene being targeted.
This design allows for a true paradigm shift: Instead of individually injecting many individual worms with different versions of a gene, researchers can inject the entire library of mutations into one worm.
Then, when the worm reproduces, the library expands. In each offspring, a book from the mutation library is randomly selected to complement the targeted gene. The result: a collection of worms that all have different randomly selected genetic mutations.
The researchers called their technique TARDIS, a playful nod to Dr. Who's space and time traveling police cabin. Here it stands for Transgenic Arrays Resulting in Diversity of Integrated Sequences.
Possible applications of editing 2.0
The researchers tested TARDIS with a gene that gives the worms resistance to antibiotics. But they see broad applications for biology in general, including research in other model organisms.
It could be particularly useful for studying interactions between proteins or signaling between cells, suggests the UO research professor Stephen Banse, which helped develop the TARDIS. Such interactions are often relevant to understanding diseases, but scientists lose important context by studying them in yeast or bacteria, Banse said.
“Now we can do these things in an animal model.” And then in man.
