Designing The Ultimate Backstage Pass to the Brain

Quick Overview

Dr. Barbara Bailus, chair of the FAST Scientific Advisory Board, discusses the development of a novel delivery system called ZIP Delivery for therapies targeting the brain. The system uses a cell-penetrating peptide, acting as a backstage pass, to allow therapies to cross the blood-brain barrier and reach neurons. The peptide, derived from the Zika virus, has been successfully used to deliver CRISPR to mouse brains, showing promise for treating neurodegenerative disorders such as Angelman syndrome. Dr. Bailus is currently working on attaching the peptide to specific proteins, including UBE3A, to address the genetic component of Angelman syndrome. The research is funded by a FAST new investigator grant.

Introduction

Dr. Barbara Bailus, the chair of the FAST Scientific Advisory Board, delivered a talk on designing the ultimate backstage pass to the brain at the 2023 FAST Science Summit. In her presentation, she discussed the development of a patented delivery system called ZIP Delivery, which utilizes a novel cell-penetrating peptide to overcome the blood-brain barrier and deliver therapies to the neurons. Dr. Bailus explained the potential applications of this technology in treating neurodegenerative disorders such as Angelman syndrome and Huntington’s disease.

The ZIP Delivery System

The ZIP Delivery system was invented at the Buck Institute, where Dr. Bailus did her postdoctoral work. It utilizes a tiny piece of the Zika virus as a cell-penetrating peptide, which acts as a backstage pass to the brain. By attaching this peptide to therapeutic agents such as CRISPR, researchers can effectively deliver them to the neurons where they are needed. The ZIP Delivery system has shown promising results in mouse models, with CRISPR being distributed throughout the entire brain after injection.

Applications in Angelman Syndrome

Dr. Bailus is currently applying the ZIP Delivery system to Angelman syndrome, a genetic disorder that affects the nervous system. By attaching the ZIP peptide to UBE3A, the gene associated with Angelman syndrome, researchers aim to replace the faulty gene and restore normal function. Initial experiments have shown that the ZIP-UBE3A complex can penetrate neuronal cells and remain active for up to 24 hours. Dr. Bailus also mentioned ongoing research on other cell-penetrating peptides that can be used to deliver different therapeutic agents.

Future Directions

Dr. Bailus outlined her plans for future experiments, including testing the ZIP-UBE3A complex in mice and evaluating the effectiveness of ZIP CRISPR for Angelman syndrome. She also expressed the need to characterize and test additional cell-penetrating peptides for different proteins. Dr. Bailus expressed her gratitude to the various labs and individuals who have contributed to this research, including her mentor Dr. Dave Segal, Dr. Lisa Ellerby, and the members of her own lab.

Conclusion

Dr. Bailus’s presentation highlighted the potential of the ZIP Delivery system in revolutionizing the treatment of neurodegenerative disorders. By designing a backstage pass to the brain, researchers can overcome the blood-brain barrier and deliver therapeutic agents directly to the neurons. The ZIP Delivery system shows promise in treating Angelman syndrome and other conditions, and further research is underway to optimize its effectiveness.