If the CRISPR gene editing system is to live up to its disease-curing potential, researchers must devise a plan to deliver it into the body
In fewer than five years, an important new gene-editing tool called CRISPR has radically changed the face and pace of biological research. The ability to quickly and cleanly remove and replace stretches of DNA has already inspired thousands of publications featuring the technique and led to the creation of a slew of biotech businesses hoping to capitalize on CRISPR.
CRISPR’s power to effortlessly target and tweak any piece of DNA seems limitless. Thomas Barnes is the chief scientific officer of the CRISPR-centered Intellia Therapeutics, whose founders include one of the inventors of CRISPR, Jennifer Doudna. He says there is “an ever-growing backlog of well-understood rare genetic conditions with little that people can do about them.” Barnes hopes CRISPR will change that.
By tackling genetic disease at its roots—mutations in the DNA—CRISPR could end thousands of ailments, Barnes and others believe. Multiple research groups and companies are hot on the tracks of unleashing CRISPR on sickle cell disease, hemophilia, cystic fibrosis, Duchenne muscular dystrophy, genetic forms of blindness, and, of course, cancer.
The hype is partly about CRISPR’s broad applicability, but CRISPR’s true promise is its potential for a one-and-done cure. Changing your DNA is a permanent fix. CRISPR—short for the “clustered regularly interspaced short palindromic repeats” in the bacterial immune system from which the technology was derived—is a two-part system: a customizable guide RNA and a protein called Cas9. The guide RNA directs Cas9 to any desired segment of DNA for editing. The Cas9 enzyme then cuts the DNA at that precise location, allowing for genes to be turned on or off or for the removal or insertion of DNA.
But editing the DNA of cells in a petri dish—or even curing a mouse of a disease—is one thing; making the hot new technology work in humans is a whole other challenge. Sneaking the gene-editing complex into human cells is no easy task.
It will take some fancy molecular maneuvering to get the bulky Cas9 protein and the negatively charged guide RNA into humans. To work its magic, the unwieldy gene-editing system first needs to get into the body, skirt past the immune system, and infiltrate its target tissue. From there, it must sneak across cell membranes, escape the acidic environment of the cell’s endosomes to find the nucleus, and then home in on the correct location on the DNA. In other words, CRISPR has a drug delivery problem.
The Cas9 enzyme and the guide RNA composing the CRISPR complex cannot be swallowed in pill form or simply injected into the bloodstream. And a one-size-fits-all package is unlikely to work for every condition, so researchers are eagerly testing old strategies and creating new ones to achieve a CRISPR cure.
David Liu of Harvard University says this delivery dilemma isn’t unusual for a new gene-editing technology, but “researchers now feel this incredible urgency and excitement because of the promise of using CRISPR for therapeutic applications.” Since its inception as a gene-editing tool in 2012, nearly 5,000 papers mentioning CRISPR have been published in PubMed. The CRISPR craze is reeling in polymer chemists, drug delivery designers, and bioengineers all helping move CRISPR from the lab bench to the doctor’s office.
“I’ve just never seen any field that progresses at this pace,” says Niren Murthy of the University of California, Berkeley, who cofounded a start-up called GenEdit, dedicated to CRISPR delivery, in February 2016. “There is nothing comparable to the competitiveness of the CRISPR field,” he says....MUCH MORE