Dr. Omar Abudayyeh Awarded Michelson Prize for Proposal to Develop RNA Therapies Against Diseases

Dr. Omar Abudayyeh entered graduate school at an exciting time. As a PhD student in the lab of Feng Zhang, one of the inventors of CRISPR/Cas9 genome editing technology, Abudayyeh got to be at the forefront of DNA modification. However, he and another student, Jonathan Gootenberg, soon found their true calling in RNA editing.  “It’s a very hot topic,” he says.

Now, Abudayyeh is a recipient of one of the 2024 Michelson Prizes: Next Generation Grants awarded by the Michelson Medical Research Foundation and the Human Immunome Project. The award will allow him to develop RNA-editing tools that could treat cancer and other diseases. 

As a therapeutic, RNA editing could have some advantages over DNA. Drug regulators are concerned about the chance that CRISPR could make edits in genes other than its intended target, potentially causing harmful mutations. On the other hand, RNA is transient by nature, and cells tend to break it down quickly, halting the production of the editing enzymes. And because RNA edits are temporary, patients might eventually be able to “upgrade” their treatment if a better editing system or disease target is discovered. “It’s like getting a new iPhone,” Abudayyeh says. 

Abudayyeh and Gootenberg, who jointly run the AbuGoot Lab, have been focusing on a set of enzymes called adenosine deaminases (ADARs) that bind to double-stranded RNA molecules and alter the letters of its genetic code. Several companies are testing them in clinical trials as treatments for genetic disorders. These approaches use a short piece of RNA that binds to a patient’s own mRNA, creating a double-strand that attracts ADARs within the recipient’s cell. The enzymes edit the transcript, essentially correcting the message from the faulty gene before the cell can make a protein. 

The $150,000 Michelson Prizes grant allows Abudayyeh to develop a new type of ADARs that could kill cancer cells or treat other conditions like sickle cell disease that only occur in a particular cell type.

Abudayyeh and Gootenberg invented a type of reprogrammable ADAR called RADARS, which detect RNA transcripts that only occur in certain types of cells. This system includes an mRNA molecule encoding a toxic protein whose genetic instructions are “locked” by a piece of code that prevents the cell from producing the protein. But if the cell contains a specific mRNA of its own -- an mRNA that is only produced by cancer cells, for instance -- the message can be unlocked, allowing the cell to make the deadly protein and die from its effects. This approach enables the researchers to target tumors without the risk of killing healthy cells by mistake. 

Initially, the pair are focusing on liver cancer, a disease for which few therapeutic options are available. It’s also a good test case for RADARS since the lipid nanoparticles that carry them into the body naturally go to the liver. They are currently testing it in cells and mice, trying to answer questions such as whether the nanoparticles are toxic to the liver and how much RNA editing is needed before the immune system jumps in to finish the cancer off. He says the technology might be ready for initial human trials in three to four years.

Eventually, Abudayyeh envisions developing RADARS into a “pan-tumor” treatment, targeting them to a few proteins that all cancerous cells produce or a RADARS platform that can easily personalize to an individual patient’s tumor. “You can literally have a single drug that you can repurpose over and over,” he says. “If we can build therapies like that, we can better accelerate treatments for the hundreds of cancers that are actually out there.”