Tetracycline repressor regulated oncolytic viruses

Inactive Publication Date: 2008-01-10
THE BRIGHAM & WOMEN S HOSPITAL INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

[0015] The amount of virus administered will vary from patient to patient but it is generally expected that between 1×106 and 1×1010 PFU (plaque forming units) will be administered at a time. Tetracycline will be administered either systemically to the patient or, more preferably, locally to the tumor either at the time of infection or 1 to 72 h prior to infection. The administration of tetracycline will have the

Problems solved by technology

As a result, gene transcription is permitted, virus replication p

Method used

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Examples

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examples

[0032] The current example describes the creation and testing of an oncolytic HSV-1 recombinant, KTR-27, which encodes two copies of the tetr gene controlled by the HSV-1 immediate-early ICP0 promoter in the ICP0 locus and the essential ICP27 gene under the control of the tetO-bearing ICP27 promoter. To reduce the levels of ICP27 expression immediately after HSV infection, a riboenzyme sequence was inserted at the 5′ untranslated region of ICP27. Alternative designs and methods will be readily apparent to those of skill in the art.

[0033] Materials and Methods

[0034] Plasmids

[0035] p27BS is an ICP27-expressing plasmid with flanking sequences 406 bp upstream of the ICP27 open-reading frame to 461 bp downstream of ICP27 poly A signal ptetO27, derived from p27BS, contains two tandem tet operators (5′-TCCCTATC AGTGATAGAGATCTCCCTATCAGTGATAGAGATCGCTGCA-3′ (SEQ ID NO:2)) at 20 bp downstream of the last nucleotide of the TATAAGG element of the ICP27 promoter. Note that the tet operator con...

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Abstract

The present invention is directed oncolytic Herpes simplex-l viruses whose replication is controlled using a tetracycline operator/repressor system. The invention also includes DNA sequences used in making the viruses and methods in which these viruses are used in the treatment of cancer patients with solid tumors.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] The present application claims priority to, and the benefit of, U.S. provisional application 60 / 819,382, filed on Jul. 10, 2006. This prior application is hereby incorporated by reference in its entirety.STATEMENT OF GOVERNMENT FUNDING [0002] The United States Government has a paid-up license in this invention and the right in limited circumstances to require the patent owner to license others under reasonable terms as provided for by the terms of NIH Grant Nos. ROIA105088 and ROIGM51449 awarded by the Department of Health and Human Services.FIELD OF THE INVENTION [0003] The present invention is concerned with oncolytic viruses, especially Herpes Simplex Virus type 1, that rely upon the tetracycline resistance (tet) operator and repressor to control their replication after the infection of tumor cells and / or normal cells. It encompasses DNA sequences used in recombinantly producing the viruses and methods in which the viruses are used i...

Claims

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Application Information

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IPC IPC(8): A61K48/00C07H21/04C12N7/01
CPCC12N7/00C12N15/86A61K35/763C12N2710/16643C12N2830/003C12N2710/16632
Inventor YAO, FENG
Owner THE BRIGHAM & WOMEN S HOSPITAL INC
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