Dr. Barbara Bailus, Keck Graduate Institute Assistant Professor of Genetics, recently received a distinguished New Investigator Grant from the Foundation for Angelman Syndrome Therapeutics (FAST) of $500,000 over two years. This grant will support a research project titled “Targeting Angelman Syndrome Therapeutics to the Brain Utilizing Novel Cell-Penetrating Peptides.”
The origins of this project can be traced back to her 2013 research which Bailus conducted as a PhD student in the lab of Dr. David Segal at UC Davis. In the lab, they designed an artificial transcription factor—a precision-tailored molecule designed to bind DNA and regulate transcription in a preprogrammed manner—to successfully treat Angelman syndrome (AS) in a mouse model.
AS is a neurodevelopmental genetic disorder that causes delayed development, a universal lack of speech, balance issues, learning disabilities, sleep disturbances, and seizures. Individuals with this disorder generally live a normal length of life and need one-to-one support.
“Caring for an individual with AS is extremely challenging as they are unable to live an independent life, requiring full-time care, but with promising therapeutics on the horizon, we are hopeful this will change,” Bailus said.
Currently, no direct treatment for AS exists; though several are in clinical trials, all one can do is manage symptoms. Bailus’s research at UC Davis focused on directly treating AS by delivering purified artificial transcription factors to the brain via a peripheral injection, activating the silent copy of the missing or non-functional gene responsible for AS.
A cell-penetrating peptide (CPP) allows one to inject the protein either subcutaneously—directly under the skin—or intraperitoneally—in the abdominal body cavity. In this manner, the therapeutic protein can cross the blood-brain barrier, entering the brain’s neurons and activating the silent gene of interest, UBE3A.
“Usually in these scenarios, you must directly inject the drug into the brain, or fluid surrounding the brain,” Bailus said. “The trick here was to find a way around that. We added a cell-penetrating peptide to the protein, which is essentially a backstage pass to the brain, carrying the protein across the blood-brain barrier and into the neurons of the brain.”
Over the two-year grant, Bailus plans to test up to three novel cell-penetrating peptides to carry the therapeutic targets into human cells and the brains of mice.
“This is a very exciting project that could change the landscape of drug delivery for neurologic disorders,” said Dr. Allyson Berent, Chief science officer for FAST. “There are many companies and stakeholders that are very much looking forward to the results of this study, and we are thrilled that the disease model being utilized to test these novel constructs is Angelman syndrome.”
Bailus has been with KGI since 2020. She teaches multiple classes, including Genetic Engineering, Genetic Disease Mechanisms, and Clinical Trial Design and Literature Evaluation for students in KGI’s genetics programs.
“I love being in the lab and doing research with my students,” Bailus said.
“I also love being in the classroom and connecting with the students. So, being a professor is perfect for me because I get to do a little of everything that I enjoy.”
Bailus particularly enjoys working with students in the lab and witnessing their excitement when they get results.
“I am very fortunate to be working in such an amazing area of research,” Bailus said. “It’s such an honor to work with the Angelman syndrome community and with an organization that’s been able to focus on actually moving into clinical trials and impacting humans living with this rare disease. I am beyond excited to get started on the research.”