University of California San Francisco
Helen Diller Family Comprehensive Cancer Center

The First Genome Surgeons: Scientists Are Preparing to Bring DNA-Editing Tools to the Clinic

By Ariel Bleicher | | October 24, 2018

The First Genome Surgeons: Scientists Are Preparing to Bring DNA-Editing Tools to the Clinic

Bruce Conklin (right), MD, is testing CRISPR-based surgeries on donated cells from Delaney Van Riper (left). These surgeries aim to cure patients like her who have rare genetic disorders. Photo by Steve Babuljak

One afternoon in July, deep within the labyrinthine halls of the Medical Sciences Building at UC San Francisco’s hilltop campus on Parnassus Avenue, the laboratory of Alex Marson, MD, PhD, is buzzing. Doors clap. Gloves snap. Keyboards clack. Cells incubate in nutrient baths the color of Kool-Aid while machines resembling rice cookers spin mixtures of molecules, separating large from small. Every now and then, a printer whirs with notes for a new experiment, like a lunch order arriving in a restaurant kitchen.

Theo Roth, an MD-PhD student, opens a deep freezer, releasing an icy cloud. Here, amid frosted boxes stacked on frosted shelves, is the impetus for all this activity  –  the reason Roth and Marson and their colleagues at UCSF and elsewhere have begun to suspect, with no small amount of excitement, that they are in the vanguard of a new era in medicine.

Roth pulls out a box and lifts from it a transparent plastic vial no taller than a toothpaste cap. Inside, he explains, are billions of intricately folded, ribbon-like molecules: proteins known as Cas9. When linked to other molecules called guide RNAs, the Cas9 proteins transform into …

“… the magic CRISPR system,” Roth says, holding the vial up to the light.

Its contents look like … well, nothing. “Just another clear liquid,” Roth jests  -  because as he well knows, these molecules’ humble appearance belies a singular and extraordinary power.

The Coming CRISPR Cures

If you’ve heard of CRISPR (pronounced “crisper”), a hot topic in science circles nowadays, you’ve likely encountered a dizzying array of definitions and divinations. Is CRISPR a therapy? A revolution? A pair of genetic scissors? A text editor? A genesis engine? A gateway to designer babies? And what does that catchy acronym  –  which stands for “clustered regularly interspaced short palindromic repeats”  –  even mean?

Put simply, CRISPR is a tool. In fact, it is many tools  –  more precisely described as CRISPR systems  –  exquisitely engineered for operating on life’s tiniest anatomy: DNA, the substance of genes. These tools aren’t the first of their kind, but they are by far the most exacting, the cheapest, and the easiest to use. Dispatched into living cells, they can be made to manipulate any gene in any tissue in any organism, whether microbe, mouse, or monkey.

Or human. Just six years after the discovery of CRISPR technology, hundreds of research labs around the world are now using it to study patients’ cells and to create animal models of human diseases  –  from common illnesses to inherited disorders so rare that they may affect only a few families. This fast-growing body of research has proven a boon to medical science, showing how DNA  –  a spiraling chain of chemical bases strung together like rungs on a ladder  –  keeps us alive and healthy, and how even subtle changes in this code can make us sick.

But for physician-scientists like Marson and young trainees like Roth, the ascendancy of CRISPR systems raises an even grander hope: If these tools can illuminate the causes of disease in the laboratory, why not bring them into the clinic to treat patients?