Frances Arnold, PhD, winner of the 2018 Nobel Prize in Chemistry, has received FAST funding to develop new molecular tools that could help develop highly durable RNA-targeted therapies for Angelman syndrome.
Dr. Arnold is the Linus Pauling Professor of Chemical Engineering, Bioengineering and Biochemistry at Caltech. She is one of the world’s leading experts in directed evolution, the Nobel Prize-winning approach she pioneered to engineer enzymes with new or improved functions.
Now, her lab is applying that expertise to Angelman syndrome.
The Science: Directed Evolution and Nucleoside Analogs
Dr. Arnold pioneered a technique called directed evolution, which uses the principles of evolution to engineer enzymes with new or improved functions. In simple terms, scientists introduce changes into enzymes, test which versions perform best, and repeat the process until they develop enzymes with the desired properties.
Nucleoside analogs are synthetic molecules with a chemically altered backbone that helps them to resist breakdown by enzymes that normally degrade RNA-like molecules in the body. That durability is one reason this chemistry is attractive for future RNA-based therapeutic development.
The challenge is that nucleoside analogs can be difficult and expensive to manufacture, which has limited how widely they can be used in therapeutics. This is now overcome with their newly engineered biocatalysts.
Dr. Arnold’s lab will use directed evolution, along with machine learning, to engineer enzymes that can help produce these types of molecules more efficiently. In practical terms, the lab is trying to use these new building blocks to build better RNA-targeting therapeutic candidates. Grant Details
Grant Title: Molecular Tuning of RNA Therapies to Treat Angelman Syndrome
PI: Frances Arnold, Caltech
Grant Type: FAST-TRAC
Grant Amount: $180,000/year
Duration: 2 years
Focus area or FAST Pillar alignment: Pillar 2
This grant is made possible with support from Maddie's Mission Foundation in partnership with the Shaw Family.
FAST-TRAC grants support targeted research projects designed to answer specific scientific questions and move promising work toward the next decision point.
Why This Matters for the Angelman Syndrome Drug Development Pipeline
This grant is part of our Pillar 2: Turn on Dad's UBE3A, therapeutic programs that focus on activating the silent copy of the paternal UBE3A gene in the brain.
Paternal unsilencing of the UBE3A gene is showing real promise for Angelman syndrome. Dr. Arnold’s project is focused on targeting the UBE3A antisense (UBE3A-ATS) using novel technology that could have long durability and broad biodistribution.
For FAST, this is exactly the kind of investment that can change what becomes possible next: bringing world-class scientific expertise to a specific challenge in Angelman syndrome drug development, then connecting that work to the next stage of testing through the FAST-funded research pipeline.
Dr. Arnold’s decision to bring her lab’s expertise to Angelman syndrome also reflects something important: as the Angelman syndrome research landscape advances, more scientists from outside the traditional Angelman syndrome community are seeing opportunities to contribute.
Progress does not depend on one idea, one therapy, or one lab. It depends on building better tools, asking better questions, and making sure promising science has a path forward. This grant helps do exactly that.
Help Move the Next Step Forward
Research like this only matters if promising ideas have a path to the next stage.
FAST is funding the tools, testing, and follow-on studies needed to move Angelman syndrome research forward with urgency. If Dr. Arnold’s lab identifies improved RNA-targeted candidates, the next step will be testing them in Angelman syndrome models through a collaborative FAST-funded lab.
Your support helps make those next steps possible.
Donate to help advance the next stage of Angelman syndrome research.