Conditionally replicative and conditionally active viruses
OwnerJohn C. Bell, David F. Stojdl +3inventors
InventorsJohn C. Bell, David F. Stojdl, Douglas A. Gray, Nahum Sonenberg, Brian Lichty
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Abstract
Viral gene constructs and modified viruses contain properties which permit them to replicate or have activity only in target cells such as diseased or otherwise infected cells.
Claims22
A virus modified to contain in its genome, a viral gene comprising two separate open reading frames (ORFs), a first of said ORFs comprising a fusion with a sequence coding for a recognition sequence for a cellular kinase protein specific to a diseased cell, and a second of said ORFs comprising a fusion with a sequence coding for a protein which binds to said recognition sequence exclusively when said recognition sequence is phosphorylated, thereby reconstituting a viral protein, said reconstituted viral protein being essential to viral replication.
A genetically modified virus comprising a gene sequence which codes for a mutated viral phosphoprotein having a phosphorylation site of a type which when non-mutated is phosphorylated by a cognate kinase, said phosphoprotein being capable of acting within a target cell such that said viral phosphoprotein is not phosphorylated by said cognate kinase, but rather is recognized solely by a kinase which is either restricted in its expression, or hyperactivated in a target cell, wherein phosphorylation of said viral phosphoprotein by said kinase is critical to viral replication thus restricting the replication of said virus to said target cell.
A genetically engineered virus containing a viral gene expressed as a fusion protein including:
- an inhibitory domain appended to a viral protein, said inhibitory domain for preventing the function of said fusion protein:
- a specific protease cleavage site between said inhibitory domain and said viral protein sequence for cleavage of said fusion protein by a specific protease contained within a target cell to yield a functional viral protein free of said inhibitory domain.
A genetically modified virus containing a plurality of cistrons, at least two of said cistrons being linked by a nucleotide sequence acting as an internal ribosome entry site (IRES) element, said IRES element being exclusively or preferentially active in a target cell population in such a way that the second of said two linked cistrons is converted to a protein product only in said target cell.
Dependencies are inferred from the claim text.