Horizons and Hope in Gene Editing

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Jackson K. Eby, PhD
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Published on Apr 26, 2024

I grew up a scientist. And I don’t mean in the "every kid is a scientist at heart" way. I mean the "I want to put the pond water under the microscope" and the "let's fly to Mars to look at the rocks" way. Everything about the scientific search for objective truth fascinated me, but the application of that truth to improving the human condition was what motivated me to pursue it as a career. It led me first to study immunology and the inner workings of vaccines to find new ones that could eradicate scourges like tuberculosis and malaria. During that pursuit, I was lucky enough to get a job developing a new application for work I was already doing: making a medicine that could precisely change the genetic code inside a living, breathing human. It was uncharted territory, totally unproven, technically challenging, and potentially life-changing for patients. I was all in.

CRISPR, short for clustered regularly interspaced short palindromic repeats, was initially discovered as a bacterial defense mechanism against viral infections. These palindromic repeats in the bacterial genome were found to flank short copies of viral genetic sequences, meaning the bacteria were able to make RNA molecules to target specific regions of viral genomes. When these RNAs were bound to a protein called Cas9, the complex could make precise cuts in viral DNA to inactivate it. The Nobel prize–winning leap was recognizing that this system could enable researchers to edit, remove, or replace genes not just in viruses, but also in the human genome to precisely treat mutations associated with genetic disorders.

When you're trying to do something so novel and challenging and you're in a race with other people to do it first, you're bound to run into the guardrails at every turn. The first publications on CRISPR showed that it worked in cells in a dish, but we didn't know if it would work in a live animal. If it did work in an animal, how relevant would that be to humans? How would we convince health regulators that it was safe enough to try? Each step on the development path required us to answer new questions about how our technologies worked, better define how we can consistently reproduce this medicine, and ensure that patients would be kept as safe as possible. The long road that turns academic discoveries into life-saving treatments is often overlooked but is so full of obstacles, pitfalls, and traps that most technologies never make it to the end goal of treating patients. Everyone working on this effort knew it could fail, but nothing ventured, nothing gained.

From these beginnings, CRISPR technology has emerged as a game-changer in the field of genetic medicine, offering hope for individuals living with rare genetic disorders. Unlike traditional therapies that often manage symptoms, CRISPR holds the potential to address the root cause of these conditions by correcting the underlying genetic mutations with a single dose of medicine. Hearing from patients with these debilitating conditions that no one outside their communities has even heard of can be both heartbreaking and inspiring.

Through this technology, a woman who must be constantly vigilant in case her throat suddenly starts swelling closed could walk into a clinic and be relieved of that worry for the rest of her life. A doctor who had to stop practicing medicine because he couldn't feel his hands any longer could see his children treated before they suffer the same fate. Knowing I’m doing my small part to transform patients’ lives is incredibly gratifying.

As promising as this technology is, the challenges facing its development are myriad. First, there are technical challenges to edit the genes in the right cells to drive the desired outcome. Sickle cell disease (red blood cells), cystic fibrosis (lung cells), and muscular dystrophy (muscle cells), just to name a few, are not all alike when it comes to developing genetic treatments. And even when we can reach the right cells, editing the human genome is not something easily or hastily done. Everyone in the field appreciates that permanent editing means for better or worse.

Ensuring the safety and efficacy of these treatments is a paramount concern, as off-target effects could pose safety risks to patients. Immense effort is spent carefully identifying potential safety concerns at every step of the development process to ensure patients receive the safest medicines possible. I find these challenges both daunting and exciting. Because the list of technologies required to make this medicine work is long and continues to grow, I can't think of a more exciting and hopeful time to be working in biotechnology.

With CRISPR technology, we stand on the cusp of a new era in medicine, one in which we can change the makeup of our own genes to turn off harmful ones or add useful ones with precision and safety. When I step back to think about what we have done in the 12 years since CRISPR was first discovered, I'm reminded of the legendary science fiction writer Arthur C. Clarke's third law: Any sufficiently advanced technology is indistinguishable from magic. We are creating magic in a vial and the world will never be the same.