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A Novel Method of Penetrating the Blood-Brain Barrier

brain, blood, the scientific student

The Blood-Brain Barrier (BBB) is a selective permeability barrier, made up of specialised endothelial cells, which does not allow blood to come in contact with the brain tissue. To protect the brain the BBB restricts diffusion of large and hydrophilic particles, drugs and pathogens, which are carried around the body in the bloodstream, into the cerebrospinal fluid. In fact, it is said to stop 95 % of medicine from entering the brain, which can be problematic for treatment of neurological conditions like Parkinson’s and Alzheimer’s. Finding a non-invasive alternative to neurosurgical intervention to deliver the medicine to a person’s brain is a current area of extensive medical research. One of the advancements includes using nanoparticles, although interactions of nanoparticles with biological systems are not yet known in full.

The California Institute of Technology claimed to have achieved a breakthrough  recently. They modified adeno-associated virus (AAV), which could “successfully enter the adult mouse brain through the bloodstream and deliver genes to cells of the nervous system.” AAV is a virus that causes a minimal immune response and can transfect genes into the target host cells. In 2009, a research group at Ohio State University found that AAV9, a variant (serotype) of AAV, can cross the BBB in neonatal mice. Interestingly, they also discovered that AAV9 yielded a widespread genetic change in the brain versus the common extremely localized change, typically observed with gene transfers. The goal of the researchers at Caltech was to extend the powers of this discovery to adult mice by altering the shape of the virus.

After genetically engineering and testing many different types of the virus for highest efficiency at crossing the BBB, the Caltech researchers chose AAV-PHP.B, which was 40 times better than AAV9. The researchers modified AAV-PHP.B to transfect cells with a gene for green fluorescence protein to tell whether or not it was working. The green pigment was spread through the brain more sparsely in AAV9 than in AAV-PHP.B transfection, which meant that AAV-PHP.B was highly effective. Furthermore, green pigment persisted for at least a year, which indicated long-term expression of the transfected genes. Using harmless viruses as vectors for drug delivery has great potential implications for the advancement of neurology, genetics and psychiatry and will help to battle a range of neurological conditions, which do not have a successful treatment at the moment.

Editor: Nelli Morgulchik