Research Press Release

Getting transgenes to the brain

Nature Methods

October 18, 2010

A simple method to deliver external genes to the mouse central nervous system is published this week in Nature Methods.

Exogenous genes, or transgenes, are frequently delivered to the brain using viral vectors, but existing methods for doing this have disadvantages. In particular, it is typically necessary to inject the vectors directly into the brain. Although some vectors do reach the brain if administered peripherally, they predominantly target non-neuronal cells and immature neurons.

Jean-Pierre Louboutin and colleagues now show that vectors derived from recombinant SV40 viruses can be injected intravenously into mice to yield efficient expression of transgenes in mature neurons in several areas of the central nervous system. This occurs in particular after administration of the organic compound mannitol to relax the blood-brain barrier.

The authors examined both standard reporters and proteins of potential therapeutic interest for their delivery to the brain using this method. They report that mature neurons in multiple regions of the cortex and spinal cord were robustly targeted. The delivery of some popular reporters, such as fluorescent proteins, remains to be optimized, however.

By permitting robust diffuse delivery of transgenes expressing several different types of proteins to mature neurons in the mouse central nervous system, this approach should simplify and enable numerous experiments in neurobiology.

DOI:10.1038/nmeth.1518 | Original article

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