Scientists hope machine will make DNA editing safer

AUSTIN, Texas – Ilya Finkelstein chuckles when recounting the origins of the project that landed the University of Texas scientist and his colleagues in the prestigious academic journal Cell.

According to a peer-reviewed article, they found a way for scientists to more safely use a new kind of gene editing technique called CRISPR — a technology that has embroiled much of the scientific world in seemingly fantastic debates, such as whether creating mushrooms that don't brown in supermarkets could lead to people creating new animals or ordering babies with designer DNA.

Finkelstein and his colleagues have developed a technique that basically makes CRISPR less likely to scramble the genes it modifies, according to their paper. They say their work could enable scientists to cure a disease such as diabetes while significantly reducing the risk of a side effect such as cancer.

As an assistant professor in the Department of Molecular Biosciences — and someone whose lab is dedicated to studying the how the human genome is linked to aging — Finkelstein had been looking for an opportunity to work with CRISPR.

The technology — whose name is short for "clustered regularly interspaced short palindromic repeats" — was discovered by scientists performing experiments on yogurt cultures. They found that bacteria have immune systems that fight viruses quite effectively. Other scientists expanded on the idea; eventually came CRISPR, which exploits the system that bacteria use to protect themselves. It allows researchers to use proteins to cut out selected segments of DNA and, if needed, insert new ones.

Scientists are still determining the various ways CRISPR molecules interact with various types of DNA. A key question: how accurate are CRISPR molecules? Do they sometimes confuse one sequence of DNA for another, snipping one instead of the other? How do you test for that?

Finkelstein is among the scientists excited about what the technique can do for humanity by, for instance, improving crop yields. But he cautions that the technology is nowhere near ready for the mind-bogglingly complex task of modifying the DNA of each cell in an adult, and is still not ready for use in human embryos.

The idea started with an expensive DNA sequencer that researchers on the floor above Finkelstein's lab have been using to analyze peoples' genes. The DNA is loaded onto special slides before being placed in the machine, which uses a chemical process to analyze the DNA. Once used, those slides were thrown away — complete with the DNA. Finkelstein saw a ready source of genetic material on which to test CRISPR.

The problem: Finkelstein had trouble finding people interested in joining the project.

"Does anyone want to earn a Ph.D. digging through the garbage?" Finkelstein joked.

But eventually, his team grew so large that three people are listed as lead authors on the paper, with another 10 as co-authors.

The fundamental challenge the team faced: compiling the mind-boggling amount of data needed to really know if CRISPR can be trusted to accomplish what its proponents say it can. To that end, Cagri Savran, a Purdue University professor working on the project, built a machine mounted on a high-resolution microscope. Scientists load the slides created by DNA sequencer and then squirt them with a solution that includes CRISPR proteins. The contraption then tracks the various proteins and their interactions with various sections of DNA.

The team hopes the work will form the basis for all sorts of CRISPR tests around the world.

The researchers envision their work being used to help prevent or cure sickness — tailoring individual gene therapies for people, as opposed to tailoring new kinds of people. The hypothetical question du jour at the lab asks: What if scientists can discover whether a particular CRISPR protein will cure a case of diabetes but also cause cancer?

Finkelstein argues that if they can, they should — even if the technology isn't perfect.