Researchers at Caltech have discovered a new mechanism whereby certain viral vectors can cross the blood-brain barrier (BBB), a protective layer that limits the entry of substances into the brain, thereby hampering research and drug development for brain disorders. The study identifies an enzyme called carbonic anhydrase IV (CA-IV) as a key player in this crossing process. This finding opens the possibility for designing more effective viral vectors for therapeutic and research purposes, enhancing drug delivery to the brain and providing insights into how emergent pathogens might exploit similar pathways.
Using a multidisciplinary approach combining protein chemistry, molecular biology, and data science, the team investigated various proteins on the BBB’s surface to identify potential facilitators of viral entry. The results highlight the diverse mechanisms that enable various engineered vectors to negotiate the BBB, offering prospects for personalized treatment strategies tailored to individual biological profiles. The research led by Viviana Gradinaru and detailed in the journal Science Advances emphasizes the potential to leverage CA-IV and other newly identified targets for the creation of advanced delivery vehicles, as well as preparing countermeasures against emerging pathogens that could compromise brain health.
