Thorsten Stafforst recalls being discouraged from pursuing his research. In the early 2010s, scientists were excited about CRISPR, a tool to change human DNA. But in Tubingen, Germany, Stafforst and other researchers were more interested in altering RNA, a chemical similar to DNA. People questioned why they’d focus on RNA when DNA editing was possible.
However, by 2012, Stafforst’s team and researchers at the University of Puerto Rico discovered how to change single “letters” in RNA using an enzyme found in nature. This idea was inspired by how octopuses and squids alter their own RNA. Although this discovery hinted at new ways to treat diseases, it didn’t receive as much attention as CRISPR at the time.
Now, over ten years later, RNA editing is rapidly growing in biotechnology. Around a dozen companies, ranging from startups to established firms, are exploring this technology. Some are showing early positive results in clinical trials, and big pharmaceutical companies like Eli Lilly and Roche are interested, too.
Proponents of RNA editing argue it could be safer and more flexible than DNA editing, potentially addressing more diseases, including those currently untreatable by genetic medicine. Michael Ehlers, CEO of RNA editing startup Ascidian Therapeutics, believes RNA editing could surpass other editing technologies.
However, RNA editing is not as proven as CRISPR, and researchers are still unsure if it will work as expected in humans. Its temporary effects might limit its benefits or require frequent treatments. As a result, companies are exploring different methods to find the most effective approach.
RNA editing works by making changes to RNA molecules, which help cells create proteins from DNA instructions. By changing one genetic “letter” in RNA, proteins can be altered. Researchers use enzymes called ADARs to make these changes, inspired by how squids change their gene expression.
Stafforst’s team and others have developed ways to guide ADAR enzymes to specific RNA spots to change protein transcription, opening new drug-making possibilities. For example, RNA editing could correct harmful gene mutations or increase lacking protein levels. Biotech companies are now trying to turn these possibilities into medicines.
Wave Life Sciences is leading in this field, using RNA editing to address a genetic disease called alpha-1 antitrypsin deficiency (AATD). Other companies like ProQr Therapeutics, Korro Bio, and startups like Airna and Shape Therapeutics are pursuing similar ideas. Each has unique approaches, from targeting different diseases to using different delivery methods.
RNA editing offers advantages over other technologies, like CRISPR, which makes permanent DNA changes that could have unintended consequences. RNA editing is reversible and may be better suited for chronic conditions or diseases with varying symptoms. Developers hope to create drugs with the power of gene editing but with more flexibility, resembling traditional medicines.
However, RNA editing still faces challenges. Current methods can only make specific single-letter changes, limiting their use. Developers don’t yet know if these edits will be effective or long-lasting in humans.
At least 11 companies are working on RNA editing therapies. Wave and ProQr are publicly traded, while others like Korro Bio and newcomers like Ascidian and Airna are startups. These companies are testing RNA editing for various diseases, from genetic disorders to cancers.
Recent developments have boosted RNA editing’s prospects. Wave reported promising early trial results for its AATD therapy, sparking optimism about the technology’s potential. Ascidian and other companies are also progressing with their trials.
Though RNA editing is still in its early stages, it holds promise for future medical applications. Researchers and companies are working to refine the technology and explore its full potential, aiming to develop treatments for a wide range of health conditions over the next two decades.