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A New Mechanism for Crossing the Blood–Brain Barrier

Research News

|

Apr 19, 2023

The blood–brain barrier (BBB) 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.

Now, a new study from Caltech has identified a previously unknown mechanism by which certain viral vectors—protein shells engineered to carry various desired cargo—can cross through the BBB. This mechanistic insight may provide a new approach to designing viral vectors for research and therapeutic applications. Understanding this and other new mechanisms could also give insight into how the brain’s defenses may be exploited by emergent pathogens, enabling researchers to prepare methods to block them.

The research was conducted in the laboratory of Viviana Gradinaru, the Lois and Victor Troendle Professor of Neuroscience and Biological Engineering and director of Caltech’s Center for Molecular and Cellular Neuroscience, part of the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech, and appears in the journal Science Advances on April 19. The study’s first authors are Timothy Shay, the scientific director of Caltech’s Beckman Institute CLOVER Center; bioengineering graduate Xiaozhe Ding; and CLOVER research associate Erin Sullivan.

Read more on the TCCI for Neuroscience website

The blood–brain barrier (BBB) 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.

Now, a new study from Caltech has identified a previously unknown mechanism by which certain viral vectors—protein shells engineered to carry various desired cargo—can cross through the BBB. This mechanistic insight may provide a new approach to designing viral vectors for research and therapeutic applications. Understanding this and other new mechanisms could also give insight into how the brain’s defenses may be exploited by emergent pathogens, enabling researchers to prepare methods to block them.

The research was conducted in the laboratory of Viviana Gradinaru, the Lois and Victor Troendle Professor of Neuroscience and Biological Engineering and director of Caltech’s Center for Molecular and Cellular Neuroscience, part of the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech, and appears in the journal Science Advances on April 19. The study’s first authors are Timothy Shay, the scientific director of Caltech’s Beckman Institute CLOVER Center; bioengineering graduate Xiaozhe Ding; and CLOVER research associate Erin Sullivan.

Read more on the TCCI for Neuroscience website

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