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US 2003/0213003 A1Published application
Transgenically produced non-secreted proteins
OwnerHarry Meade, Li-How Chen +1inventors
InventorsHarry Meade, Li-How Chen, Paul DiTullio
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OwnerHarry Meade, Li-How Chen +1inventors
InventorsHarry Meade, Li-How Chen, Paul DiTullio
Estimating the term…
The invention provides a method of making and secreting a non-secreted protein. The method includes expressing the protein from a nucleic acid construct which includes: (a) a mammary epithelial specific promoter; (b) a milk protein specific signal sequence which can direct the secretion of a protein; (c) optionally, a sequence which encodes a sufficient portion of the amino terminal coding region of a secreted protein to allow secretion in the milk of a transgenic mammal, of the non-secreted protein; and (d) a sequence which encodes a non-secreted protein, wherein elements (a), (b), optionally (c), and (d) are preferably operatively linked in the order recited. Both glutamic acid decarboxylase (GAD) and myelin basic protein (MBP), which are cytoplasmic proteins, have been produced by the methods of the present invention. The invention also provides methods for treating diabetes and multiple sclerosis using proteins produced by the methods of the present invention.
A method of making and secreting a non-secreted protein comprising expressing the protein from a nucleic acid construct which comprises:
An isolated nucleic acid construct which comprises:
A method for providing a non-secreted protein in the milk of a transgenic mammal, comprising obtaining milk from a transgenic mammal having introduced into its germline a nucleic acid construct comprising a heterologous non-secreted protein-coding sequence operatively linked to a milk protein specific signal sequence and a mammary epithelial specific promoter sequence that result in the preferential expression of the protein-coding sequence in mammary gland epithelial cells, thereby secreting the heterologous non-secreted protein in the milk of the mammal
A method of inducing tolerance in a subject to an antigen, comprising:
A method of treating insulin-dependent diabetes mellitus (IDDM) in a subject, comprising administering to the subject therapeutically effective amount of a transgenically produced tolerogen which comprises glutamic acid decarboxylase, or an effective amount of a fusion protein which comprises glutamic acid decarboxylase.
A method for treating multiple sclerosis in a subject, comprising administering to the subject therapeutically effective amount of a transgenically produced tolerogen which comprises myelin basic protein, or an effective amount of a fusion protein which comprises myelin basic protein.
A therapeutic composition which comprises a therapeutically effective amount of the transgenically produced myelin basic protein and a pharmaceutically-acceptable carrier or diluent.
A fusion protein which comprises:
A method of inducing tolerance in a transgenic mammal to an antigen,
A transgenically produced non-secreted polypeptide, wherein the polypeptide is secreted.
The transgenically produced non-secreted polypeptide of claim 51, wherein the cytoplasmic polypeptide is glutamic acid decarboxylase or myelin basic protein.
Dependencies are inferred from the claim text.