Peptide biosynthesis and pain therapy

摘要

The invention provides an expression cassette comprising a DNA sequence encoding amino acids 1-99 of human preproenkephalin, a DNA sequence encoding a precursor of a carboxy-amidated peptide flanked by dibasic cleavage sites and optionally a DNA sequence encoding a marker protein (such as Enhanced Green Fluorescent Protein (GNP)) all in operable linkage and under control of a promoter. Where the encoded precursor of a carboxy-amidated peptide is an agonist for an opioid receptor, the invention further provides a method of treating neuropathic pain by administering the gene transfer vector comprising such an expression cassette to a patient. The invention also provides a method for detecting a peptide having a desired effect comprising introducing a library of DNA sequences encoding one or more precursors of carboxy-amidated peptides into host cells; expressing the carboxy-amidated peptides encoded in the library to provide expression products; and screening from the polypeptide expression products for the desired effect.

主权项

1. A genetic expression cassette comprising:
(a) a first DNA sequence encoding a regulated secretory pathway preproprotein signal sequence; (b) a second DNA sequence encoding a precursor of a peptide flanked by cleavage sites, wherein the second DNA sequence does not encode for the corresponding endogenous peptide of the first DNA sequence; and (c) optionally a third DNA sequence encoding a biomarker protein; wherein the first, second, and optional third DNA sequence are in frame relative to each other.