Intrinsic system for viral vector transgene regulation
AssigneeThe Vaccine Group Limited
InventorsMichael JARVIS, Alex REDWOOD
Life of this patent
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Abstract
A method for the regulated removal of heterologous genetic material from disseminating viral vaccine vectors is provided.
Claims31
1-20. (canceled)
A method for the regulated removal of heterologous genetic material from disseminating viral vaccine vectors, comprising:
- providing a wild-type or parental viral vector which includes a recombinantly engineered duplication of genomic sequence;
- providing a transgene expression cassette which comprises a transgene and the necessary regulatory genetic elements for control of transgene expression flanked by copies of a region of the wild-type or parental genomic sequence;
- inserting the cassette into the vector so that the transgene is flanked by the wild-type or parental genomic sequence and its duplicated sequence;
- whereby homologous recombination subsequently results in removal of the transgene to leave only a single copy of the homology sequence as is normally found within the wild type or parental virus, thereby regenerating the wild-type or parental virus genome with an absence of any non-parental virus genetic sequence;
- and
- selecting a length of the duplicated sequence;
- in which the rate of transgene removal from the viral genome, and hence reversion of recombinant virus genome to wild-type or parental, is a function of the length of the selected duplicated sequence.
A method for the rapid removal of heterologous sequences from genetically modified viruses, comprising:
- providing a wild-type or parental viral vector which includes a duplicated sequence of the viral genome of a preselected length;
- providing an expression cassette which comprises a transgene and necessary regulatory sequences and a copy of a duplicated region of the wild-type or parental sequence;
- and
- inserting the cassette into the vector so that the transgene is flanked by the wild-type or parental sequence and its copy of a defined size;
- whereby homologous recombination results in removal of the transgene to leave only a single copy of the flanking homology sequence thereby regenerating the wild type or parental virus genome.
A method for the rapid removal of heterologous genetic material from disseminating viral vaccine vectors, comprising:
- providing a wild-type or parental viral vector which includes a duplicated sequence of genome of a preselected length;
- providing an expression cassette which comprises a transgene and a copy of the wild-type/parental flanking sequence;
- inserting the cassette into the vector so that the transgene is flanked by the wild-type or parental sequence and its duplicated region of the genome;
- whereby homologous recombination results in removal of the transgene to leave only a single copy of the flanking homology sequence thereby generating the wild type or parental virus genome with an absence of any non-viral genetic sequence, both in terms of sequence and copy number.
A wildlife vaccination system for a transmissible vaccine, the vaccine comprising a viral vector having a transgene flanked by a duplication of viral genome sequence for allowing homologous recombination between repeated sequences and concomitant excision of the transgene and leaving only a single copy of the duplicated flanking region comparable to that found within the wild type/parental genome, in which transgene expression persistence is a function of the length of the duplicated genomic sequence, the size and nature of the transgene such that the length of transgene expression is definable and variable, whereby a non-permanent presence of the recombinant virus within the environment is provided.
A viral vector having a transgene flanked by duplicated viral sequences for allowing homologous recombination between the duplicated sequences and concomitant excision of the transgene and leaving only one of the two duplicated sequences thereby returning the virus to a generally wild type or parental genome state, in which transgene removal from the vector is a function of the length of the duplicated sequences.
A method for the regulated removal of heterologous genetic material from vaccine vectors, comprising:
- providing a wild-type or parental viral vector which includes a recombinantly engineered duplication of genomic sequence of a preselected length;
- providing an expression cassette which comprises a transgene and the necessary regulatory genetic elements for control of transgene expression flanked by copies of a region of the wild-type/parental genomic sequence;
- inserting the cassette into the vector so that the transgene is flanked by the wild-type or parental genomic sequence and its duplicated sequence;
- whereby homologous recombination results in removal of the transgene to leave only a single copy of the homology sequence as is normally found within the wild type or parental virus, thereby regenerating the wild type or parental virus genome with an absence of any non-parental virus genetic sequence;
- in which the rate of transgene removal from the viral genome, and hence reversion of recombinant virus genome to wild-type or parental, is a function of the length of the duplicated sequence.
Dependencies are inferred from the claim text.