How Gene Editing Is Changing the Way We Treat Genetic Disorders

2024

David Liu, a prominent molecular biologist, is leading a revolution in gene editing that promises to reshape the future of medicine. As a professor at the Broad Institute of MIT and Harvard, Liu has developed two groundbreaking technologies—base editing and prime editing—that offer unprecedented precision in altering the DNA sequence, paving the way for more effective treatments of genetic diseases.

Liu's work was recently recognized with the prestigious Breakthrough Prize in Life Sciences, awarded for his contributions to gene-editing technologies. Liu plans to use the $3 million prize to support his charitable foundation, which funds further research and initiatives in the field.

DNA is made up of four chemical bases—A, G, T, and C. Mutations in these sequences can cause a variety of genetic disorders. Historically, gene-editing technologies have been limited in their ability to correct these mutations. CRISPR-Cas9, for example, can cut the DNA but often introduces errors during the repair process, making it more effective at disrupting genes than correcting them.

Base editing, developed by Liu’s team, offers a solution by using a modified Cas9 protein that avoids cutting both strands of the DNA. This allows the technology to precisely convert one base to another—such as changing a C to a T or a G to an A—without the risk of creating new errors. Liu’s team has shown that this method can correct about 30% of the mutations known to cause genetic diseases. The first clinical trials involving base editing have shown promising results, including a breakthrough treatment for AATD, a rare genetic disorder that affects the lungs and liver.

Despite its success, base editing cannot address all types of genetic mutations. To expand its capabilities, Liu and his team introduced prime editing in 2019. This technique allows for the correction of longer stretches of faulty DNA, including insertions or deletions of base pairs, making it more versatile than base editing. Prime editing works similarly to a word processor’s "find and replace" function, offering the ability to rewrite DNA with greater accuracy.

Prime editing has already been used to target diseases like cystic fibrosis, which is caused by a missing section of DNA. In one of the most notable trials, Liu’s team demonstrated how prime editing could correct the mutation responsible for cystic fibrosis, providing hope for future treatments. The technology has since been made freely accessible to the scientific community, allowing researchers around the world to build on Liu’s work.

While base editing and prime editing have shown considerable promise in treating genetic diseases, there are still challenges to overcome. Prime editing, for instance, is still limited in its ability to edit larger stretches of DNA, and delivering these tools to the right parts of the body remains a significant hurdle. Liu’s team is working on methods to deliver these molecular tools to specific tissues, such as the heart, liver, and brain, using viral vectors and other innovative strategies.

Looking ahead, Liu is focused on developing treatments for rare genetic diseases, which collectively affect hundreds of millions of people globally. These diseases, often overlooked because they are divided into many different conditions, could be treated using the advanced tools Liu has developed. His goal is to create mutation-agnostic therapies that can address multiple genetic mutations at once, offering a universal treatment option for patients with various genetic disorders.

The impact of Liu’s work extends beyond human medicine. He has also applied gene-editing technologies to agriculture, co-founding the company Pairwise Plants, which uses base editing to create crops that are more nutritious and resistant to diseases.

Liu’s contributions to science have been widely recognized. His work has not only advanced gene-editing technologies but also shifted the landscape of medicine, providing new possibilities for the treatment of genetic diseases. However, he remains quick to credit his team of students and collaborators, acknowledging that their efforts have been integral to the success of these groundbreaking technologies.

In his acceptance speech for the Breakthrough Prize, Liu emphasized the importance of supporting scientific institutions, particularly the National Institutes of Health, which faces challenges under the current administration. He expressed concern over efforts to dismantle the funding systems that support critical research and innovation in the United States.

David Liu’s work represents a significant step forward in gene editing, and as research continues, it holds the potential to transform how genetic diseases are treated, offering hope to millions of people worldwide.