CRISPR/Cas9: How a new genome-editing tool could help patients

Scientists have made great strides in gene therapy over the last decade. Patients are already benefitting from technologies that add new genes or correct misbehaving ones, but concerns still linger about these procedures’ safety and cost. Since 2013, researchers at HSCI and MIT have been developing an alternative genome-editing tool, called the CRISPR/CAS9 system, which may address some of gene therapy’s hurdles. This new approach to altering genomes was inspired by nature, specifically , bacteria.

The bacterial immune system

Bacteria may be germs, but they can also catch a virus. Viruses that latch onto a healthy bacterium will inject their genetic code into their victim. The code integrates itself into the bacterium’s DNA and transforms the bacterium’s genetic machinery into a virus factory. The bacterium soon fills with newly formed viruses and bursts.

In the 2000s, researchers found that bacteria that carry the CRISPR gene locus—more than half of all bacteria—seemed to have more immunity to viruses. Upon closer inspection, scientists learned that CRISPR allows these bacteria to incorporate the DNA from a virus into their own genomes, in a way building a memory of an infection. Bacteria use this information and an enzyme, Cas9, to target viral DNA and chop it up.

“It’s an adaptive immune system for bacteria,” said HSCI Principal Faculty member Chad Cowan, PhD, a co-founder of startup CRISPR Therapeutics. “And it didn’t take long for some very smart people to consider that it might possible to use this CRISPR/Cas9 system to cleave the mammalian genome.”

A discovery in Cambridge

Harvard geneticist George Church, PhD, and Feng Zhang, PhD, working independently at the MIT and Broad Institute, were the first to translate CRISPR/Cas9 technology into mammalian cells. They demonstrated how to guide the Cas9 enzymes to the genome of a human or mouse cell and cause the DNA to break, allowing any mutation to be made or repaired.

“People use it all the time now in human cell lines,” Cowan said. “People at Harvard have been trying to use this system as a gene therapeutic tool, where you could direct the CRISPR/Cas9 system to correct a mutation that’s causing a disease.”

Current and future applications

In 2013, the HSCI iPS Core began to offer CRISPR/Cas9 genome editing in addition to reprogramming services. “It’s wonderful because you no longer have to spend years or months of a postdoc’s time to make these cells,” said Cowan, who also acts as the Core’s Co-director.

Several HSCI faculty members are already taking advantage of the resource, exploring how the tool can help patients with diabetes, HIV, or sickle-cell anemia, as well as those susceptible to heart attacks.

A June 2014 study from Kiran Musunuru, PhD, and colleagues in Harvard’s Department of Stem Cell and Regenerative Biology showed that using CRISPR/Cas9 to mutate a gene in the livers of mice could reduce cholesterol levels, which over the lifetime of the individual would prevent heart attacks by up to 90 percent.

According to Professor Cowan, expect more exciting discoveries to be published in the months to come.