JOINT EXPRESSION OF GTP CYCLOHYDROLASE AND TYROSINE HYDROXYLASE

摘要

The invention provides novel genetically modified host cells, vectors, and methods for the treatment of Parkinson's disease and other related disease conditions in which the dopamine production is deficient. The invention relates to the surprising discovery that coexpression of tyrosine hydroxylase and GTP cyclohydrolase enables host cells to produce elevated dopamine and L-DOPA without adding tetrahydrobiopterin and that the coexpression of GTP cyclohydrolase stabilizes tyrosine hydroxylase. One embodiment of the invention is genetically modified host cells containing heterologous polynucleotide sequences encoding and capable of expressing GTP cyclohydrolase and tyrosine hydroxylase. Other embodiments of the invention include genetic construction that contain and can simultaneously express polynucleotide sequences encoding a GTP cyclohydrolase and a tyrosine hydroxylase. The invention also provides methods of producing L-DOPA or dopamine using the host cells of the invention. The invention also provides methods of treating patients of Parkinson's disease or other diseases related to a dopamine production deficiency using the vectors and methods of the invention.