The
subject matter of the present invention is a delivery vector comprising
a DNA sequence encoding pro-predynorphin or a variant of pro-predynorphin and wherein said delivery vector drives the expression of pro-predynorphin in a target
cell and wherein said delivery vector comprising said
DNA sequence is capable of releasing predynorphin or a variant of predynorphin from a target
cell as needed, and wherein the pro-pro-
peptide is pro-pro-
peptide or a pro-pro-
peptide variant and wherein the pro-pro-peptide comprises a
signal peptide wherein the
signal peptide is an N-terminal extension of a neonatal
polypeptide chain and wherein the
signal peptide mediates a
protein targeting an endoplasmic network lumen, and wherein the pro-peptidogen comprises an N-terminal pro-peptidogen fragment on the C-terminus of the
signal peptide and wherein the N-terminal pro-peptidogen fragment (i) comprises a sorting motif comprising elements DL and EXyL, in particular a sorting motif consisting of the
amino acid sequence DLXxEXyL, or comprising ii) a sorting motif of pro-neuropeptidic or
protein sorted into a dense core macrovesicle, except for pro-prodynorphin as defined herein, where in certain embodiments, x is an integer from 1 to 20, y is an integer from 1 to 10, and each instance of X may independently be any
amino acid, such as any
amino acid, or any amino acid, such as any amino acid, or any amino acid, such as any amino acid, or any amino acid, such as any amino acid, or any amino acid, such as any amino acid, or any amino acid, such as any amino acid, or any amino acid. And wherein the N-terminal pro-peptidic fragment consists of 16 to 90 amino acids, as well as corresponding peptides,
DNA molecular viral vectors and particles comprising any of these.