Targeted delivery of glycine receptors to excitable cells
The invention provides a method of modulating electrophysiological activity of an excitable cell. The method involves causing exogenous expression of a glycine receptor (GlyR) protein in an excitable cell of a subject. Thereafter, the excitable cell is exposed to an allosteric modulator of the GlyR protein. Modulation of the exogenous GlyR protein (an ion channel) in response to the allosteric modulator modulates the electrophy-stological activity of the excitable cell. The method can be used to control pain in a subject. The invention further provides a replication-defective HSV vector comprising an expression cassette encoding a GlyR protein, stocks and pharmaceutical compositions containing such vectors, and a transgenic animal.
1. A replication-defective HSV vector comprising an expression cassette encoding (i) a glycine receptor (GlyR) protein consisting of an alpha 1 subunit of GlyR and (ii) an expression control sequence that promotes the expression of the GlyR protein in peripheral neurons, wherein the HSV vector provides for the attenuation of pain sensation in a subject when administered to such peripheral neurons.
2. A viral stock comprising the vector of claim 1 having a titer of between about 10 6 plaque-forming units (pfu) and about 10 11 pfu.
3. A pharmaceutical composition comprising the vector of claim 1 and a pharmaceutically-acceptable carrier.
4. The pharmaceutical composition of claim 1 , formulated for injection.
5. The vector of claim 1 , wherein at least one of the peripheral neurons is a c-fiber.
6. The vector of claim 1 , wherein the subject is human.