by Buck Institute

The Buck’s Impact Circle supports a project aimed at delivering therapeutic “cargoes” across the blood brain barrier

The Buck’s Impact Circle donor group has announced its choice for 2023. This year it is supporting a project aimed at tackling a major challenge in the medical field: how to deliver therapeutics across the nearly impervious blood brain barrier.  The group’s $100,000 award will enable Buck professor Lisa Ellerby, PhD, and former Buck postdoctoral fellow Barbara Bailus, PhD, to work on further developing their novel delivery system to bring various therapeutics into the brain, and they are hijacking the “good” parts of the Zika virus to do it.

Dr. Lisa Ellerby

Dr. Barbara Bailus

“Many thanks to the Impact Circle for supporting our project,” says Ellerby, a neuroscientist whose lab studies Alzheimer’s and Huntington’s diseases. “The award will allow us to move our patented technology from proof of concept to the pre-clinical safety studies that are needed before starting a new company and embarking on human trials.”   For her part, Bailus welcomes the opportunity to continue working on a project that she and Ellerby conceived before Bailus left the Buck to become an assistant professor of genetics at the Keck Graduate Institute in Claremont, CA.  “I love being able to continue collaborating with Lisa and others at the Buck. Her expertise in neuroscience and my specialty in genetics make us perfect partners for this effort.”

Here are the basics of the project: 

The blood brain barrier is a specialized and intricate network of blood vessels and vasculature that walls off the brain, making it nearly impossible for molecules to penetrate it.  While this is a good thing for keeping harmful molecules at bay, it is a major obstacle when there’s a need to deliver therapeutics to the brain.  Current delivery systems are invasive (involving spinal taps or directly drilling into the brain), non-specific (they can go anywhere in the body), and can potentially result in a negative immune response.

Ellerby and Bailus have designed a new cell-penetrating protein that can act as a “key card” that allows therapeutics to pass through the blood brain barrier and infiltrate the brain.  Their invention utilizes a fragment of the Zika virus, which is able to get into neurons and neuronal tissues. Preliminary research shows that the Zika fragment can be used to deliver therapeutic technologies through the blood brain barrier.  The technology has been dubbed “ZIP (Zika-Integrated Peptide) Delivery.”  (Mainly spread via mosquito bites, a Zika infection is fairly benign in most humans, but a Zika infection during pregnancy can cause a birth defect of the brain called microcephaly.) 

“ZIP Delivery is minimally invasive; it’s a single targeted IV injection with widespread brain distribution,” said Ellerby.  “It can be titrated and will not linger, reducing the chances of harmful side effects.”  Ellerby and Bailus have used ZIP Delivery to deliver various proteins into neuronal cells.  They’ve also put it into brain organoids (cultured from human pluripotent stem cells) and into mice, where it showed widespread distribution into the brain including the hippocampus, where memories are consolidated. 

The Ellerby/Bailus team will use the Impact Circle award to produce and test the safety of ZIP-delivery in mammalian cells and they’re focused on fixing the mutation that causes Huntington’s disease to do it. “We picked Huntington’s because the disease is caused by a single genetic mutation so it’s a simple place to start,” said Bailus, who adds the project also includes delivering and validating a 2nd non-protein method for ZIP Delivery into the brain. “In addition to proteins, ZIP Delivery can potentially be added to lipid nanoparticles, viral particles, nucleic acids and antisense oligonucleotides.  All of them can be used for therapeutic benefits.” 

“We are so excited to explore the potential of ZIP Delivery,” said Ellerby. “I can see it being used to treat a number of neurological diseases, as well as being used proactively to protect our brains from the ravages of aging. We might be able to deliver proteins to reduce brain inflammation or introduce proteins known to increase longevity.   Given its potential impact, this is a perfect project for the Impact Circle.”  

The Impact Circle is still welcoming new members. Click here to become a member. Established in 2014, the Impact Circle is a peer group of like-minded philanthropists who advance scientific discovery at the Buck by pooling their resources to provide seed money for early stage projects. In addition to the satisfaction of supporting ground-breaking research (and tracking its success), they also get a front row seat on the scientific process.  Previous awards have focused on efforts to support brain resilience, the role of oxytocin in aging, and exploring whether extremely long-lived queen honeybees can inform research on human aging. If you would like to learn more, contact Lisa Palma, Director of Philanthropy at lpalma@buckinstitute.org.


Science is showing that while chronological aging is inevitable, biological aging is malleable. There's a part of it that you can fight, and we are getting closer and closer to winning that fight.

Eric Verdin, MD, Buck Institute President and CEO

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