How CRISPR Tools are Unlocking New Ways to Fight Disease

Even as these new CRISPR tools hint at new avenues for gene therapy, they’re already opening the field for other therapies by revealing the complex genetic interactions that underlie diseases.

The most immediate payoff may be in identifying new therapeutic targets, according to Bruce Conklin, MD, professor of medicine at UCSF and senior investigator at Gladstone Institutes, who works with CRISPRi and related techniques in his research.

“The power of these techniques is to test thousands of different drug targets in a single experiment. This has already helped with leads for potentially useful drugs,” he said.

It’s estimated that 98 percent of our DNA does not code for proteins, but instead act as a switchboard for the 2 percent that do. These so-called promotors and enhancers can be cryptic and time-consuming to study with conventional genetic techniques.

With CRISPRa, Marson’s lab can rapidly screen over 20,000 non-coding sites in the genome and study their function — essentially by flipping many switches and seeing which ones turn on the lights. “This is a critical step in identifying the functional significance of genetic elements,” said Marson.

In a recent CRISPRa screen, Marson’s lab, in collaboration with the lab of Jacob Corn, PhD, at UC Berkeley, identified several enhancers associated with inflammation and autoimmune disorders. In fact, one of the newly identified enhancers matched a common genetic variant known to increase the risk of irritable bowel disease, although its mechanism had previously been a mystery.

Lim has watched the CRISPR-dCas9 methods he helped pioneer disperse to research labs around the world in just a few years. From 2013 to the end of 2015, 49 papers included the term dCas9 in their title or abstract, according to PubMed. From 2016 through June 2018, 242 papers cited the same term — a nearly five-fold increase.

“It is amazing how quickly this technology has spread within just a few years.” said Lim. “It speaks to how flexible the simple core concept is.”

Gene editing is already providing new therapies for rare diseases that just a generation ago were untreatable. New techniques with CRISPR hold promise for greatly improving both quality and length of life for those suffering from genetic conditions.