Molecular Tuning of Next-Generation Oligonucleotides to Treat Angelman Syndrome
Molecular Tuning of Next-Generation Oligonucleotides to Treat Angelman Syndrome
Our cells use DNA and RNA as instruction manuals to make proteins that our body needs to function. In disorders like Angelman syndrome (AS), errors in DNA or RNA can lead to the wrong instructions. This can result in the body producing too much, too little, or non-functional proteins. This can cause serious health problems. Scientists have developed special treatments called antisense oligonucleotides (ASOs) to help fix these mistakes. ASOs are made by stringing together building blocks called bases. Current
drugs that are being developed for AS use specialty bases, chemistries and modifications to improve the drug delivery and penetration to cells. These ASOs in the clinic need to be injected directly into the spinal fluid multiple times a year because they are metabolized and don't last more than a couple of months after the injection. Theoretically, these drugs can be modified through chemical reactions and new building blocks. This team aims to engineer the enzymes to make new building blocks with more efficiency. The learnings may provide researchers with new opportunities for next generation ASO therapies that last longer.
Principle Investigator
Frances Arnold, PhD
Frances Arnold is the Linus Pauling Professor of Chemical Engineering, Bioengineering, and Biochemistry at the California Institute of Technology. She was awarded the Nobel Prize in Chemistry in 2018 for pioneering directed enzyme evolution and has used directed protein evolution for applications in alternative energy, chemicals, and medicine. Her lab is developing new methods of machine-learning guided enzyme evolution and exploring non-natural enzyme reactivities. Her work has been recognized with numerous awards, including the Charles Stark Draper Prize of the National Academy of Engineering (2011), the National Medal of Technology and Innovation (2011), and the Millennium Technology Prize (2016). She has been elected to the National Academies of Science, Medicine, and Engineering and was appointed to the Pontifical Academy of Sciences by Pope Francis in 2019. She served as co-chair of President Biden’s Council of Advisors on Science and Technology from 2021-2025. Arnold earned her BS in Mechanical and Aerospace Engineering from Princeton University and PhD in Chemical Engineering from the University of California, Berkeley.
