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.
Claims112
A polynucleotide, comprising:
- a nucleic acid encoding a recombinant protein;
- a modified post-transcriptional regulatory element (PRE) operably linked to said nucleic acid, said modified PRE comprising a variant of a wild-type hepatitis virus X gene, said variant X gene comprising a stop codon not present in the wild-type 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 stop codon not present in the wild-type X gene, wherein the stop codon comprises at least one stop codon selected from among:
- a stop codon beginning at a position within 32 or 30 nucleotides in the 3′ direction from a position in the variant X gene corresponding to the 5′ position of a start codon of the wild-type X protein open reading frame;
- and/or
- a stop codon beginning at a position within 32 or 30 nucleotides in the 3′ direction from a position in the variant X gene corresponding to residue 411 of WHV post-transcriptional regulatory element (WPRE) sequence set forth in SEQ ID NO:
- 1 and/or residue 1503 of the WHV sequence set forth as SEQ ID NO:
- 2.
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.
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.