Modified hepatitis post-transcriptional regulatory elements
AssigneeJuno Therapeutics, Inc.
InventorSemih U. Tareen
Life of this patent
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Abstract
Provided are polynucleotides containing a modified PRE having a variant X gene that includes one or more stop codons not present in an unmodified, such as wild-type, hepatitis X gene. Also provided are polynucleotides containing a modified PRE having a variant X gene that includes one or more degradation sequences not present in an unmodified, such as wild-type, hepatitis X gene. The modified PRE can be operably linked to a nucleic acid encoding a recombinant protein. Also provided are expression cassettes, viral vectors and cells containing the polynucleotides, and compositions and methods of use thereof.
Claims46
A polynucleotide, comprising a modified post-transcriptional regulatory element (PRE), said modified PRE comprising a variant of a wild-type hepatitis virus X gene, said variant X gene comprising a plurality of stop codons not present in the wild-type X gene, wherein the variant X gene comprises a stop codon in each reading frame present in said variant X gene.
A polynucleotide, comprising a modified post-transcriptional regulatory element (PRE), said modified PRE comprising a variant of a wild-type hepatitis virus X gene, said variant X gene comprising a plurality of stop codons not present in the wild-type X gene;
- and,
- a nucleic acid encoding a recombinant protein that is a recombinant receptor operably linked to the modified PRE.
A polynucleotide, comprising a modified post-transcriptional regulatory element (PRE), said modified PRE comprising a variant of a wild-type hepatitis virus X gene, said variant X gene comprising a plurality of stop codons not present in the wild-type X gene, wherein said stop codon is selected from among:
- a stop codon beginning at a nucleotide position corresponding to position 420 in the sequence set forth in SEQ ID NO:1;
- a stop codon beginning at a nucleotide position corresponding to position 424 in the sequence set forth in SEQ ID NO:1;
- a stop codon beginning at a nucleotide position corresponding to position 428 in the sequence set forth in SEQ ID NO:1;
- and
- a stop codon beginning at a nucleotide position corresponding to position 432 in the sequence set forth in SEQ ID NO:1.
A polynucleotide, comprising a modified post-transcriptional regulatory element (PRE), said modified PRE comprising a variant of a wild-type hepatitis virus X gene, said variant X gene comprising a sequence encoding a post-translational modification signal not present in the wild-type hepatitis virus X gene.
A polynucleotide, comprising a viral nucleic acid comprising a variant Flap, wherein the variant Flap contains a deletion of all or a portion of the nucleotides corresponding to the central polypurine tract (cPPT) and/or the central termination sequence (CTS) regions of a wild-type or unmodified Flap sequence.
Dependencies are inferred from the claim text.