CRISPR, the new genome-editing tool, has already saved thousands of lives — but chances are you won’t meet any of the survivors.
That’s because they’re lab mice.
Scientists have been using dramatically fewer mice for each experiment since the advent of the groundbreaking technology. CRISPR, short for clustered regularly interspaced short palindromic repeats, allows researchers to cut and paste bits of DNA, almost as if they were words on a computer screen. And when geneticists first turned to CRISPR to create mice in 2013, they found that it provided a quicker, cheaper alternative to the traditional mouse-making technology.
Whereas the old method, which relied on genetically engineered stem cells, could take as long as a year to produce a mouse strain, a new model can be created in just weeks at a fraction of the cost.
“It’s a much easier and simpler procedure,” said Haoyi Wang, a gene-editing expert at the Jackson Laboratory in Maine, one of the biggest producers of lab mice in the country.
Already, CRISPR-made mice have been used to better understand how a number of simultaneous genetic mutations come together to cause diseases, why some tumors are more sensitive to certain drugs, and the way certain genes contribute to memory formation in the brain.
It was a pain to make these kinds of model mice with embryonic stem cells. These cells are the embryo’s raw building materials. When they proliferate, they can turn into any other kind of cell in the body. That meant they could be manipulated genetically and then used to deliver targeted mutations into mouse embryos.
But stem cells are finicky creatures, hard to keep alive. And using them to make mice wasn’t simple.
After tweaking a gene in an embryonic stem cell, scientists still had to inject the stem cell into an embryo, implant the embryo into a mother mouse, and breed the resulting offspring with each other until they obtained a strain that expressed the manipulated DNA in all its cells.
If scientists also wanted to combine different mutations in a single mouse, or needed to get rid of a harmful mutation that had snuck in on their stem cell’s DNA, they then had to spend months mating mice together. Only after breeding for 10 generations — requiring well over 100 mice — did they get the model their experiment required.
All that breeding was a headache for researchers. And CRISPR is providing the aspirin.
Instead of using an embryonic stem cell as a vehicle, with CRISPR, scientists can squirt a genetic cocktail — containing strands of genetic material and a special DNA-cutting enzyme called Cas9 — straight into the embryo. Do the injection while the embryo is still a single cell, implant the whole shebang into a mother, and the mutation should take root in her babies.
“This is an incredibly efficient way to do things,” said Guoping Feng, a neuroscientist at the Massachusetts Institute of Technology. “And you save a lot of animals.”
But before animal activists pop the champagne, they should remember that a more efficient way to create mutant mice also means more experiments.
“It’s a double-edged sword,” said Lisa Garrett, a geneticist at the National Human Genome Research Institute. “We don’t require as many for each experiment, but now everyone can make knockout mice.”
“A lot of companies are going CRISPR-crazy and making mice.”