"The ability to engineer AAV capsids with improved transduction efficiency, specificity, and tropism for particular cell types or brain regions has opened up new opportunities for gene therapy in the brain."
Adeno-associated virus (AAV) gene therapy has emerged as a promising approach for treating a range of neurological and psychiatric disorders, including Parkinson's disease, Huntington's disease, and Alzheimer's disease. However, one of the key challenges in developing effective AAV gene therapy for the brain has been the ability to target specific regions of the brain with high precision.
To address this challenge, researchers have been developing engineered AAV capsids that can target specific regions of the brain. These engineered capsids are designed to have specific properties that enable them to bind to and enter certain types of cells or cross certain barriers in the brain.
One strategy for developing engineered AAV capsids involves the use of directed evolution, a process in which AAV capsids are mutated and selected for their ability to target specific cell types or regions of the brain. As a review article in Nature Neuroscience notes, "Directed evolution has generated AAV capsids that can transduce specific subtypes of neurons, astrocytes, and oligodendrocytes in vitro and in vivo, as well as capsids that can cross the blood-brain barrier and selectively target regions of the brain, such as the striatum and hippocampus."
Another approach to engineering AAV capsids involves the use of rational design, in which researchers use knowledge of AAV structure and function to design capsids with specific properties. For example, a study published in Nature Biotechnology reported on the development of an AAV capsid that was able to cross the blood-brain barrier and selectively target neurons in the substantia nigra, a region of the brain that is affected in Parkinson's disease.
In addition, researchers have been exploring the use of AAV capsids that are modified with targeting ligands, such as antibodies or peptides, that can bind to specific receptors on the surface of cells in the brain. A study published in Science Translational Medicine reported on the use of an AAV capsid modified with an antibody fragment that was able to target and transduce specific populations of neurons in the brain.
Overall, these engineered AAV capsids offer a promising approach for developing highly targeted gene therapies for neurological and psychiatric disorders. As a review article in Annual Review of Neuroscience notes, "The ability to engineer AAV capsids with improved transduction efficiency, specificity, and tropism for particular cell types or brain regions has opened up new opportunities for gene therapy in the brain."
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