UOUO) A new gene editing technology developed by researchers has compressed work that previously took years to just a few days, allowing new research on animal models. It will allow biologists to experiment with comparing multiple versions of genes, looking for mutations that lead to specific traits and track their evolution over time.
Such studies are often the first step in identifying mutations related to human health or revealing the mechanisms behind human diseases.
Although large-scale gene editing technology has been developed for single-cell organisms such as bacteria and yeast , this is the first time this scale has been achieved in animals.
"In biology , we spend a lot of time studying gene mutants. But in animals, we are limited by how many gene mutants can be made at a time," said Zach Stevenson, a graduate student in Patrick Phillips' lab. Who helped design this technology. "This is a way to get around this bottleneck."
Stevenson and his colleagues described their new technology in a preprint published to bioRxiv.
They have tried the system in Carean elegans , a small worm that is popular in biological research. Similar methods can eventually be applied to other experimental animals, such as flies or mice, Stevenson said.
“Genogenetic engineering of microbial DNA has been the foundation of the biotechnology revolution for the past three decades, but it is difficult to do on a large scale in animal systems,” Phillips said. "The new approach developed in our lab could serve as a platform to use simple animals in a completely new way as the basis for synthetic biology , just as bacteria and yeast have been around for a generation."
Scientists may hope to be able to produce many gene mutations at the same time. For example, they may be looking for a mutation that makes animals resistant to specific drugs, or be able to survive better under certain conditions, or are less susceptible to disease. They may need to screen dozens or even hundreds of possible genetic variants to find the most effective variants. Experiments like
are very slow in animals. Each mutant strain—a group of worms with specific genetic modifications—must be designed separately. Stevenson said making a mutant “usually takes seven to ten hours of hands-on time.” Using this new system, "the same labor can make three or four mutations, you can make tens of thousands."
To speed up, Stevenson and his colleagues have designed a way to compress hundreds or even thousands of possible mutations into a "library." Every book in the library is a small piece of genetic code , which itself is meaningless and invalid. Each piece fits an engineering gap in the target gene, like a library puzzle with genes crazy.
This design means that instead of injecting different versions of genes into many individual worms, researchers inject the entire pool of mutations into a single worm.
Then, as the worms reproduce, the library expands. In each offspring, a book is randomly selected from the mutation library to complete the target gene. When a part of gene bank slides in, it activates the gene, just like a toggle switch to complete the circuit.
Results: A series of worms have different randomly selected gene mutations.
Researchers named their technology TARDIS—a fun homage to Dr. Who’s time travel police station. Here, it represents a series of transgenes that lead to the integration sequence diversity . Like the fictional TARDIS, the worm is “larger inside”, Stevenson said. (That is, it contains a lot of additional genetic material.)
researchers tested TARDIS with a gene that confers nematode antibiotic resistance. But they have seen widespread applications of biology, including research on other -mode organisms, .
UO research professor Stephen Banse, who helped develop TARDIS, said it may be particularly useful for studying interactions between protein or signaling between cells.Banse said this interaction is often associated with understanding diseases, but scientists have lost important background by studying them in yeast or bacteria. "Now we can do these things in animal models."
