CRISPR’s growing presence in the world of genetically engineered research mice.

Much of the hope and the hype surrounding the gene editing technology CRISPR (clustered regularly interspaced short palindromic repeats) is its potential to treat and cure diseases. The most significant development came a few weeks ago when the first proposed human test of CRISPR passed a key safety hurdle in the US.

But CRISPR or CRISPR-Cas9 as it is usually referred to, is also impacting how we generate animal research models of disease. Historically, creating transgenic mice that express certain mutations has been a long and costly process that has frustrated scientists. CRISPR-Cas9 technology greatly reduces the time it takes to do the work—in roughly 5-6 weeks you can have your mice—and offers scientists an unprecedented amount of flexibility to engineer more animals and to study such animals in more complex and diverse ways.

What this ultimately means for the field of preclinical research is unclear. CRISPR-Cas systems, which in nature helps bacteria defend against attacking viruses called phages, has emerged as one of the most effective methods of tweaking or knocking out gene function. Science listed it as their Breakthrough of the Year.

CRISPR-Cas9 is clearly a game-changer for genetically modified mouse research, but the technology may also be triggering an uptick in the use of research animals at a time when laboratories are supposed to be committed to reducing the size of their colonies. Figuring out how to communicate the purpose and value of CRISPR-Cas9—how it works and why it’s important in animal research—to non-scientists will also be a challenge, and it’s not clear which group is best positioned to take on that role.

This Wild West environment worries molecular geneticist Prem Premsrirut, who founded and leads Mirimus, a company that produces genetically-engineered mouse models, but she predicts that once the technology settles in, the field will settle down. “Right now there is a lot of excitement, and people are trying things for the sake of trying things,” said Premsrirut during her talk on Tuesday at the Charles River Short Course. “But at some point we’ll reach a plateau and we’ll develop some standardized protocols and the process will become more effective and efficient.”

Mirimus produces genetically-engineered mouse models with reverse gene silencing abilities by harnessing the power of RNA interference. It was founded six years ago by a team of scientists from Cold Spring Laboratory on Long Island and Harvard University who wanted to push the boundaries of RNA interference that organisms use to regulate gene expression.

Premsrirut said Mirimus is now working on a system for inducible CRISPR/Cas9 expression in vivo that would allow greater control over when mutations are added to mice.  One of the current problems with CRISPR-Cas9 technology is that unintended mutations may occur when CRISPR-Cas9 cleaves other DNA sequences within the genome that are homologous to the target DNA sequences. These off-target mutations can lead to embryonic death or developmental defects.

David Fischer, Executive Director of Biology and DMPK Discovery, who also gave a talk on CRISPR technology at the Charles River meeting, says the Broad Institute has developed a tool that reveals which RNA sequences guiding the insertion or deletion of DNA are best paired with the CRISPR-Cas9 in order to study the genome, and what the chances are that you will get an off-target mutation.

How to Cite:

McEnery, Regina. Clip Art. Eureka blog. June 29, 2016. Available: http://eureka.criver.com/clip.art/