Gene therapy is a great weapon against many neurological conditions, but delivering your payload into the brain is a challenge. A new vector could fix this problem
One of the best methods to deliver any gene therapy is with a viral vector. These are modified viruses that have had the harmful parts taken out, but are still really good at injecting material into cells. We now have a number of different vectors designed for different organs, but the brain is still one of the hardest areas to target with any therapy. This is because of the blood-brain barrier, a selective blood filter which stops things like viruses getting in.
"One has to drill a hole through skull, then pierce tissue with a needle to the injection site. The deeper the injection, the higher the risk of hemorrhage. With systemic injection, using the bloodstream, none of that damage happens, and the delivery is more uniform"
Sneaking past the barrier
In the past gene therapy strategies for the brain involved an unpleasant injection and drilling a hole through the skull, but scientists at Caltech have now engineered a viral vector that can successfully enter the brain of a mouse and target the nervous system. To do this, they used a modified form of an adeno-associated virus (AAV). AAVs are already common in gene therapy research, because they're some of the safest vectors around and generally avoid a harmful immune response.
“By figuring out a way to get genes across the blood-brain barrier, we are able to deliver them throughout the adult brain with high efficiency”
This is a welcome development, as many neural disorders are wide-spread throughout the brain and not localised in one area alone which an injection would target. This type of vector can deliver therapies in a uniform manner to multiple brain regions.
How did they do it?
In 2009 a strain of AAV called AAV9 proved effective in infant mice but failed in adults. Building on AAV9, they created million of copies of the virus with a slightly altered protein coating. After painstaking testing of these millions of variants, they stumbled on a form which could better enter the brain and deliver genes most effectively to astrocytes. This was termed AAV-PHP.B
“We could see that AAV-PHP.B was expressed throughout the adult central nervous system with high efficiency in most cell types. What provides most of AAV-PHP.B’s benefit is its increased ability to get through the vasculature into the brain. Once there, many AAVs, including AAV9 are quite good at delivering genes to neurons and glia”
This system obviously needs more research before moving into human trials, but the system the researchers used to find a more efficient viral form could be repeated for many areas of the body.
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