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AssigneeSmithKline Beecham Corporation
InventorsBrian Huber, Cynthia A. Richards, Elizabeth A. Austin
Estimating the term…
Novel molecular chimaeras produced by recombinant DNA techniques are described. They comprise a target-tissue specific transcriptional regulatory sequence (TRS) linked and controlling the expression of a heterologous enzyme, for example Varicella Zoster Virus Thymidine Kinase (VZV TK) or non-mammaliam Cytosine Deaminase (CD). A molecular chimaera is packaged into a synthetic retroviral particle that is capable of infecting mammalian tissue. This, in turn, may be administered to a host, and the TRS will be selectively transcriptionally activated in the target tissue (for example cancerous cells). Administration of compounds that are selectively metabolised by the enzyme produce cytotoxic or cytostatic metabolites in situ thereby selectively killing or arresting the growth of the target cells.
A molecular chimaera comprising a transcriptional regulatory sequence capable of being selectively activated in a mammalian target tissue, a DNA sequence operatively linked to the transcriptional regulatory sequence and encoding a heterologous enzyme, the enzyme capable of catalysing the production of an agent toxic to the target tissue.
A method of treating cancerous cells comprising administering to said cells, a DNA sequence capable of being selectively activated in said cells to express an enzyme, and administering an agent which is converted in said cells by said enzyme to an agent which is cytotoxic or cytostatic to said cancer cells.
A method of treating cancerous host cells comprising administering to a host an infective virion encapsidating a retroviral shuttle vector comprising a molecular chimaera, said chimaera comprising a transcriptional regulatory sequence which is selectively activated in cancerous cells and operatively linked to a gene encoding a heterologous enzyme;
A molecular chimaera comprising a transcriptional regulatory sequence selected from the group consisting of albumin, alpha-fetoprotein, and carcinoembryonic antigen;
A molecular chimaera comprising a transcriptional regulatory sequence selected from the group consisting of albumin, alpha-fetoprotein or carcinoembryonic antigen;
A molecular chimaera comprising a DNA sequence encoding the gene for E. coli cytosine deaminase operatively linked to the transcriptional regulatory sequence for carcinoembryonic antigen.
A gene delivery system comprising a molecular chimaera, said chimaera comprising a transcriptional regulatory sequence for carcinoembryonic antigen which is selectively activated in cancerous cells and operatively linked to the coding sequence for the gene encoding cytosine deaminase.
An infective virion comprising a retroviral shuttle vector, said vector comprising a molecular chimaera, said chimaera comprising a transcriptional regulatory sequence for carcinoembryonic antigen which is selectively activated in cancerous cells and operatively linked to a gene encoding cytosine deaminase.
A packaging cell line comprising a retroviral or adenoviral shuttle vector said shuttle vector further comprising a molecular chimaera.
A method of treating a host in need of anticancer treatment comprising administering to said host, a molecular chimaera capable of being selectively activated in cancerous cells of said host to express the enzyme cytosine deaminase, and subsequently administering to said host 5-fluorocytosine which is converted in said cells by said enzyme to 5-fluorouracil which is cytotoxic or cytostatic to said cells.
A method of treating a host in need of anticancer treatment comprising administering to said host an infective virion encapsidating a retroviral or adenoviral shuttle vector comprising a molecular chimaera, said chimaera comprising a transcriptional regulatory sequence which is selectively activated in cancerous cells of said host and operatively linked to a gene encoding the heterologous enzyme cytosine deaminase;
A method of treating a host in need of anticancer treatment comprising administering to said host a packaging cell line, said packaging cell line further comprising a retroviral or adenoviral shuttle vector capable of producing an infective virion, said shuttle vector comprising a molecular chimaera, said chimaera comprising a transcriptional regulatory sequence which is selectively activated in cancerous cells of said host and operatively linked to a gene encoding the heterologous enzyme cytosine deaminase;
A method of constructing a molecular chimaera comprising linking a DNA sequence encoding cytosine deaminase to a tissue-specific promoter selected from the group consisting of ALB, AFP or CEA.
A method of killing or arresting the growth of cells comprising delivering a molecular chimaera into said cells, said chimaera expressing a heterologous enzyme in said cells and exposing said cells to an agent which is converted by said enzyme to an agent which is cytotoxic or cytostatic to said cells.
A plasmid selected from the group consisting of pCR92, pCR105, pCR113, pCR136, pCR137, pCR145, pCR148, pCR158, pCR162, pCR163, pEA001, pEA002, pEA003, 39-5-2 and 39-5-5.
The clone BA101.
The isolated DNA of SEQ ID NO:4.
Dependencies are inferred from the claim text.