Glaxo Wellcome Inc.

Smithkline Beecham Corporation

Cynthia A Richards

Brian Huber

Michael Phillip Weiner

Elizabeth A Austin

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.

Molecular constructs with a carcinoembryonic antigen (CEA) transcriptional regulatory sequence

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.

Molecular constructs containing a carcinoembryonic antigen regulatory sequence

Molecular constructs comprising a carcinoembryonic antigen (CEA) transcriptional regulatory region

The present invention provides a system for simple generation of recombinant animal viruses. The system includes a virus homing vector and can further comprise a transfer vector. These components are used in a system that reduces the number of cloning steps and provides for easier preparation of a number of recombinant viruses.

System for generating recombinant viruses

The transcriptional regulatory sequence (TRS) of Carcinoembryonic Antigen (CEA) and molecular chimeras comprising the CEA TRS and DNA encoding a heterologous enzyme are described. Such molecular chimeras are capable of targeting the expression of the heterologous enzyme to CEA-positive cells. The heterologous enzyme may be cytosine deaminase.

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Durham, NC, United States of America

Cynthia A Richards