Caltech researchers discovered an enzyme that enables viral vectors to cross the blood-brain barrier, potentially aiding brain disorder drug development and research. The blood–brain barrier (BBB) is a stringent, nearly impenetrable layer of cells that guards the brain, protecting the vital organ
In a new study from Caltech, researchers have identified a previously unknown mechanism that allows certain viral vectors to cross the blood-brain barrier . The blood-brain barrier protects the brain from toxins and bacteria but also limits the study of the brain and development of drugs to treat brain disorders. The team discovered that an enzyme called carbonic anhydrase IV enables some viral vectors to cross the BBB.
The blood–brain barrier is a stringent, nearly impenetrable layer of cells that guards the brain, protecting the vital organ from hazards in the bloodstream such as toxins or bacteria and allowing only a very limited set of small molecules, such as nutrients, to pass through. This layer of protection, however, makes it difficult for researchers to study the brain and to design drugs that can treat brain disorders.
A timely approach to discovering putative BBB transporters: Directed evolution yields diverse AAVs with enhanced brain potency. BBB-specific membrane proteins are identified and screened in vitro for their ability to boost AAV potency. Computational methods enable high-throughput target screening and reverse engineering of novel viral, protein, and chemical tools.
Though the BBB serves as the brain’s formidable defense, certain viruses have naturally evolved the ability to bypass it. For decades, researchers have studied how to use these viruses as a kind of BBB-crossing Trojan Horse; to do so, researchers scrape out the original viral cargo carried by the viruses and then use their hollow shell to ferry beneficial therapeutics or tools for research.
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