Recombinant adenoviruses carrying transgenes
AssigneeEpicentRx, Inc.
InventorsChristopher Larson, Bryan Oronsky, Tony R. Reid
Life of this patent
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Abstract
Disclosed herein are recombinant adenoviruses with one or more nucleotide sequences inserted between two viral transcription units, formulations comprising the recombinant adenoviruses, and methods of treatment using the recombinant adenoviruses. In some embodiments, the one or more nucleotide sequences are inserted in an IX-E2 insertion site and/or an L5-E4 insertion site.
Claims17
A recombinant adenovirus comprising a nucleotide sequence inserted in an IX-E2 insertion site, wherein the IX-E2 insertion site is located between the stop codon of adenovirus IX gene and the stop codon of adenovirus IVa2 gene, wherein the nucleotide sequence comprises a promoter, a transgene, and a second polyadenylation signal and the recombinant adenovirus comprises in a 5′ to 3′ orientation:
- (i) a first polyadenylation signal;
- (ii) a fourth polyadenylation signal;
- (iii) the promoter;
- (iv) the transgene;
- (v) the second polyadenylation signal;
- and
- (vi) a third polyadenylation signal;
- wherein the transgene is operably linked to the promoter,
- wherein the second polyadenylation signal is the polyadenylation signal of the transgene, and
- wherein the fourth polyadenylation signal is in the opposite transcriptional direction of the first polyadenylation signal.
A recombinant adenovirus comprising a first nucleotide sequence inserted in an IX-E2 insertion site and a second nucleotide sequence inserted in an L5-E4 insertion site, wherein the IX-E2 insertion site is located between the stop codon of adenovirus IX gene and the stop codon of adenovirus IVa2 gene, and wherein the L5-E4 insertion site is located between the stop codon of adenovirus fiber gene and the stop codon of ORF6 or ORF6/7 of adenovirus E4 gene, wherein the first nucleotide sequence comprises a first promoter, a first transgene, and a third polyadenylation signal and the recombinant adenovirus comprises in a 5′ to 3′ orientation:
- (i) a first polyadenylation signal;
- (ii) a fourth polyadenylation signal;
- (iii) the first promoter;
- (iv) the first transgene;
- (v) the second polyadenylation signal;
- and
- (vi) a third polyadenylation signal;
- wherein the first transgene is operably linked to the first promoter,
- wherein the second polyadenylation signal is the polyadenylation signal of the first transgene, and
- wherein the fourth polyadenylation signal is in the opposite transcriptional direction of the first polyadenylation signal.
Dependencies are inferred from the claim text.