Kingsman, Alan John; Kingsman, Susan Mary;

Therapeutic Gene

Polynucleotide sequences and vectors containing them, for use in gene therapy, the polynucleotide sequences comprising two or more therapeutic genes operably linked to a promoter and encoding a fusion protein product of the therapeutic genes. The fusion protein may be for example a tyrosine hydroxylase (TH)-DOPA decarboxylase (DD) fusion in either TH-DD or DD-TH order, useful for treating Parkinson's disease.

• Handlebar timing device Trailer hitch
• Solid state storage device Self sealing gasket assembly
• Battery terminal post protector Automobile power door latch
• Liquid laundry detergent Infrared intrusion detector
• Quantum computer Bottle and nipple brush
• Hand winch Grain carrying vehicle
• Semiconductor pressure sensor Raw sewage drying apparatus
• Laser correcting mirror Low tension winding apparatus
• High recovery sonic gas valve High-speed cycle clock-synchrounous memory device
• Pipe positioner Printing mechanism
• Table game Turn-table dual hoisting crane
• Universal ink jet drafting film Switch apparatus
• Printing device and roll paper Cylinder servomotor
• Therapeutic Gene Fungicidal N-(substituted thio)-pyridyl cyclopropane carboxamides
• Flow control system Methods for chromosome-specific staining
• Attractant composition for synanthropic flies Surface modifications for enhanced epithelialization
• Balance shaft assembly Engine throttle body
• Portable sandwich preparation apparatus Preparation of n-aryl- and n-hetarylhydroxylamines
• Suppressory agents against hypercoagulation Electroplating process
• Rotary body position control apparatus Pipe connection
• Anticounterfeit magnetic metallized labels

What is claimed is:

1. A lentiviral-based vector capable of transducing a non-dividing cell, said vector comprising a sequence encoding a fusion protein, said sequence comprising two or more therapeutic genes operably linked to a promoter.

2. The vector according to claim 1, wherein the fusion protein is encoded by a sequence comprising tyrosine hydroxylase and a sequence encoding DOPA decarboxylase, wherein the sequences encoding tyrosine hydroxylase and DOPA decarboxylase are operably linked by a sequence encoding a flexible linker.

3. The vector according to claim 1, wherein the lentiviral-based vector comprises a lentviral LTR-deleted vector.

4. The polynucleotide sequence according to claim 1, wherein the flexible linker comprises glycine-serine amino acid repeats.

5. The vector according to claim 1, comprising a single transcription unit comprising the sequences encoding tyrosine hydroxylase and DOPA decarboxylase.

6. A method for producing a bifunctional fusion protein in a non-dividing cell, said method comprising:

providing a non-dividing cell;

transducing the non-dividing cell with the vector according to claim 1; and

expressing the bifunctional fusion protein in the cell, wherein the bifunctional fusion protein comprises tyrosine hydroxylase and DOPA decarboxylase.

7. A target cell in vitro, comprising the lentiviral vector of claim 1.

8. The vector according to claim 5, wherein the single transcription unit is under transcriptional control of the 5' LTR.

9. A lentiviral vector comprising a sequence encoding a fusion protein comprising tyrosine hydroxylase and DOPA decarboxylase, wherein tyrosine hydroxylase and DOPA decarboxylase are operably connected by a flexible linker.

10. A method for producing a bifunctional fusion protein comprising tyrosine hydroxylase and DOPA decarboxylase in a neuron, said method comprising:

providing a neuron;

transducing the neuron with the vector according to claim 9; and

expressing the bifunctional fusion protein in the neuron, wherein the bifunctional fusion protein possesses the activity of both tyrosine hydroxylase and DOPA decarboxylase.

11. The method according to claim 6, wherein the non-dividing cell is a neuron.