Reviews | We can cure disease by modifying a person’s DNA. Why aren’t we?

Across the sector of for-profit companies that manufacture gene therapy drugs, a sobering process is taking place. Even when they create a treatment that works, companies price it exorbitantly (about $2-3 million per patient), arguing that a one-time treatment saves the healthcare system years of supportive care. expensive.

For diseases with less than 100 patients, such prices are still not enough to make these efforts make commercial sense, as demonstrated by a biotechnology company, bluebird bio. After 20 years of designing such gene therapies and significant success in the clinic, bluebird bio is now struggling to remain solvent – ​​even though its price of its most recent approved drug was $3 million. Another gene-editing biotech company recently halted clinical trials for a rare disease with 300 patients in the United States, saying it could not economically justify continuing the experiments. For a disease that affects a person, the current for-profit system therefore makes building a gene therapy or gene-editing treatment a daunting challenge.

‌To make CRISPR cures a reality, the biomedical community must start with regulation. For treatments developed for genetic diseases that affect tens of thousands of people (or, say, if a company is trying to fight heart disease, which affects millions of people), the Food and Drug Administration has a process well-established review that has been around for years. But the FDA needs to consider a new regulatory process that could create a more streamlined path to bring much-needed CRISPR drugs tailored to patients with a unique genetic typo. There is precedent for this: Beginning in the late 1990s, the FDA facilitated regulatory pathways for the innovation of a new class of genomic cancer drugs – CAR-T therapy – which is now widely used. in clinic. The same can be done for CRISPR.

However, streamlining regulations will not be enough. Where will the funding come from to develop remedies for isolated patients? Biotech companies are unlikely to do this voluntarily, given the financial cost, although the for-profit sector could make a significant contribution by sharing technologies and resources that would accelerate this effort. Tapping into federal and state funding could pave the way forward. Recently, the FDA greenlighted a clinical trial designed by my colleagues at UC Berkeley’s Institute for Innovative Genomics, in collaboration with physicians from UCLA and UCSF, for an approach to genetic editing of sickle cell disease. My sense of pride in this achievement is diluted by the realization that ours is the only one of its kind. fully academic trial in the entire gene-editing space. To truly realize the potential of this technology, there would need to be dozens such ongoing efforts.

This approach asks a difficult but essential question: why should the average taxpayer contribute to the manufacture of drugs for rare diseases? Would the money be better spent on finding treatments for common illnesses?

Investing public funds in CRISPR treatments for rare diseases will not only help us treat people with rare mutations (a global community numbering hundreds of millions of people), but can also provide information that can be integrated into the CRISPR clinical innovation for common diseases.

But for the next few years, devastating genetic diseases and cancer are where CRISPR clinical trials must stay; ethical considerations on the safety of patients exposed to new technologies dictate this. Today’s tools are also akin to the first iPod – at the time, an exhilarating but still low-tech advancement over today’s smartphones. Everything we learn about how to edit people’s genes through this work, coupled with continued CRISPR innovation in the academic and for-profit sector, will provide a foundation for better understanding how to safely edit DNA. to treat and potentially prevent serious common diseases.