Cell-specific gene therapy using as promoter novel promoters for tissue inhibitors of metalloproteinase-3
AssigneeHoechst Aktiengesellschaft
InventorsHans-Harald Sedlacek, Marisa Wick, Rolf Muller
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Abstract
The invention relates to promoter sequences for a gene comprising a tissue inhibitor of metalloproteinase-3 (TIMP-3). This inhibitor is found in particular in macrophages, synovial cells, and connective tissue cells. The invention also relates to cell-specific gene therapy of a subject, wherein expression of a gene in a tissue is regulated by the aforementioned promoter sequence operationally coupled to said gene. The promoter may also be used in diagnostic methods.
Claims16
An isolated promoter for the gene of a tissue inhibitor of metalloproteinase-3, comprising promoter-active DNA fragments located in the 5'-flanking region of the human TIMP-3 gene and which are sufficient for transcriptional control of said TIMP-3 gene.
An isolated promoter for the gene of a tissue inhibitor of metalloproteinase-3, comprising promoter-active DNA fragments located within nucleotide position -500 to position +101, of the polynucleotide depicted in FIG. 2 (SEQ ID NO:
- 1).
A composition, comprising a gene operationally coupled to a promoter and an acceptable carrier, wherein said promoter comprises promoter-active DNA fragments that are located in the 5'-flanking region of the human TIMP-3 gene and are sufficient for transcriptional control of said TIMP-3 gene.
A method for regulating the expression of a gene in vitro, comprising:
- (a) providing said gene operationally coupled to a tissue human TIMP-3 inhibitor promoter;
- (b) transferring said operationally coupled gene to a cell in vitro;
- and
- (c) expressing said genes wherein said expression is increased in the presence of serum in the culture medium.
Dependencies are inferred from the claim text.