This ‘CRISPR craze’ has descended on labs across the country. Find out more about this cutting edge lab technique and how Joslin is making use of it to fight diabetes.
What if you could cut out the part of your genetic code that caused diabetes or its complications? Researchers at Joslin Diabetes Center are doing just that in experiments to better understand the genes behind diabetes.
They are using a technique called CRISPR (pronounced “crisper”). CRISPR is a gene editing tool that allows researchers to precisely modify DNA, erasing mutations in genes and replacing them with healthier variations. The technique shows huge promise not just for diabetes, but for any diseases with causes that can be traced to the genes.
Though there has been some futuristic talk about using gene editing on humans, in the real world of today’s science, CRISPR is used to modify laboratory animal models for specific research into the role genetics play in diseases like diabetes. Researchers start at the earliest stage of a mouse embryo. They decide where to snip in the DNA of a cell based on which gene they want to modify, and if they want to remove the gene altogether or replace it with something else. DNA is made up of four different bases—A, T, C, and G—that work together to create a unique individual. These bases are strung together in different ways to make genes. CRISPR works by allowing researchers to cut and remove a string of those bases, effectively removing the gene from action. Once that genetic change is made in an embryo, DNA without that gene will propagate throughout the body as the mouse grows and develops.
“It’s just a cut and paste mechanism, if you like,” says Stephan Kissler, Ph.D., Investigator in the Section on Immunobiology at Joslin Diabetes Center and Assistant Professor of Medicine at Harvard Medical School. “You can use this to introduce new genes or mutate genes.” He is working with Amy Wagers, Ph.D., Investigator in the Section on Developmental and Stem Cell Biology at Joslin Diabetes Center and Professor of Stem Cell and Regenerative Biology at Harvard Medical School, to create a gene editing core at Joslin to give researchers further access to this cutting edge process.
They use an enzyme called CAS-9 to home in on the exact location they want to cut. There are a few ways to achieve a result. Researchers can disrupt the function of a gene by snipping once in the middle of the DNA code and allowing it to repair itself. The repair will be imperfect, preventing the gene from doing its job. Or they can insert a new, better functioning gene where they made the single cut by guiding the DNA to repair itself based on a template.
For more drastic changes, they can remove a large chunk of DNA entirely. “You can make a big cut as if you had two scissors and you took a piece of string and you cut it in two places and then you drop out the piece in the middle,” he says. “And then the DNA will be repaired and you’d be left with the DNA as it was minus the piece you just cut out.
This precision technique has been useful in labs trying to understand the exact functions of the different genes that operate and malfunction in diabetes.
Check back next week for an exploration of how CRISPR is being used in Joslin labs.