"This structural 'footprint' we found seems to help these viruses get efficiently into the brain, which informs the design of potentially safer brain-targeted gene therapies," said study senior author Aravind Asokan, PhD, associate professor of genetics.
The study, published in Molecular Therapy, examined adeno-associated viruses (AAVs), the most commonly used virus vectors for delivering gene therapies. The natural forms of these small viruses normally infect people without causing disease. For gene therapies, scientists remove most of the AAV genome, replace it with therapeutic genetic cargo, and inject trillions of copies into the patient.
Principle - Scientists - AAVs - Cell - Others
In principle, scientists can modify AAVs to infect some cell types more than others to deliver their therapeutic payloads where they are most needed. However, most AAVs cannot easily cross from the bloodstream into the brain. Like most other viruses, they tend to be blocked by the cells that tightly line brain capillaries to form the so-called blood-brain barrier.
"To achieve therapeutic effects in the brain, AAVs sometimes have to be given in high doses, which raises the possibility of dose-dependent toxicity," said first author Blake Albright, a graduate research assistant at UNC.
Study - Albright - Asokan - Colleagues - Features
For the study, Albright, Asokan and colleagues tried to isolate the features that enable AAVs to cross the blood-brain barrier more easily. They started with two known AAVs, one that doesn't efficiently cross the blood-brain barrier, and one that does. They created a small library of new variants of these AAVs by swapping short stretches of DNA from one to the other. They then tested these for their ability to cross the blood-brain barrier in mice.
In this way they isolated a closely spaced set...
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