A groundbreaking gene-editing startup, Aurora Therapeutics, has been co-founded by renowned scientist Jennifer Doudna to develop personalized treatments for rare genetic diseases. The initiative follows a remarkable case in which an infant, known as KJ, received a customized gene-editing therapy designed to correct a specific genetic mutation. This treatment, which was created in just six months, addressed a condition that was causing toxic ammonia to accumulate in KJ’s body. Following the procedure, KJ was discharged from the hospital in June 2023, marking a significant milestone in the potential of gene editing.
Aurora Therapeutics aims to capitalize on a new regulatory framework introduced by the Food and Drug Administration (FDA). This pathway, termed the “plausible mechanism pathway,” allows for the approval of personalized treatments based on data from a limited number of patients. Traditionally, new drugs require extensive testing involving hundreds or thousands of participants, a challenge particularly pronounced in trials for rare diseases where patient populations are often small. According to Marty Makary and Vinay Prasad, authors of a recent article in the New England Journal of Medicine, successful outcomes in several patients will lead the FDA to consider granting marketing authorization for these innovative therapies.
The initial focus of Aurora Therapeutics will be on treating phenylketonuria (PKU), a metabolic disorder typically identified at birth. PKU affects approximately 13,500 individuals in the United States, resulting in dangerous levels of phenylalanine in the bloodstream if not managed properly. Patients must adhere to a strict low-protein diet to prevent cognitive impairments and developmental delays. As Edward Kaye, CEO of Aurora Therapeutics and a pediatric neurologist, explains, “There are a lot of patients that could benefit from this therapy. But the problem is, you have many, many mutations—over a thousand—that cause this disease.”
Gene editing technology, particularly the CRISPR system, allows for precise modifications to DNA. In KJ’s case, scientists crafted a guide RNA that directed an editing molecule to his specific genetic mutation, resulting in a treatment uniquely suited to him. Aurora’s strategy involves creating multiple versions of PKU therapy by adjusting the guide RNA to target different mutations. Previously, each variant would have been treated as an entirely new drug, necessitating separate clinical trials. The new FDA pathway allows Aurora to streamline this process, facilitating the development of therapies for various mutations linked to PKU.
Using a method known as base editing, Aurora plans to enhance the precision of its treatments while establishing a standardized process for therapy design and manufacturing. Co-founder Fyodor Urnov, who is also a genome editing scientist at UC Berkeley, emphasizes the company’s commitment to ensuring that “no mutation is left behind.” Urnov and his colleagues at the Innovative Genomics Institute, which Doudna founded in 2015, played a pivotal role in developing KJ’s treatment. The Institute will continue to explore tailored gene-editing therapies for children with rare diseases.
In parallel, a trial is being conducted at the Children’s Hospital of Philadelphia to test the same gene editing approach used in KJ’s treatment on a broader group of patients with similar disorders. The establishment of Aurora Therapeutics is seen as essential for making these cutting-edge treatments available to a larger patient population.
Despite the promise that CRISPR technology holds, its journey has not been without challenges. Several companies operating in the CRISPR space have reduced their workforce or ceased operations in recent years. To date, there is only one approved CRISPR-based drug on the market, Casgevy, which was launched in December 2023 at a price of $2.2 million to treat sickle cell disease and beta thalassemia.
Nonetheless, Urnov expresses optimism about the future of gene editing, stating, “We are finally at a place where CRISPR on demand has had all the technical problems worked out.” He anticipates that within three to four years, more children will benefit from personalized gene-editing therapies, paving the way for a new era in the treatment of rare genetic diseases.
