Synthetic cancer-specific promoters
AssigneeEARLI Inc.
InventorsDariusz Wodziak, Shireen Rudina, Maggie C. Louie, Yue Zhang, Elizabeth Stroebele, Albert Park, David Suhy, Paul Escarpe, Cyriac Roeding, Justin Lin, Alex Harwig, Leland Harrison Hartwell
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Abstract
Described herein are synthetic promoters and/or enhancers that are specific for cancer cells and methods of engineering synthetic cancer-specific promoters.
Claims47
A method for increasing expression of a gene in a cancer cell as compared with a non-cancer cell, the method comprising, administering a recombinant polynucleotide to a subject with cancer, wherein said recombinant polynucleotide comprises:
- a) one or more synthetic response elements comprising one or more enhancers and a plurality of transcription factor binding sites;
- b) a core promoter operably linked to an open reading frame (ORF) comprising said gene, wherein said core promoter comprises a promoter element obtained from one or more cancer-responsive genes;
- and
- c) a transcription start site (TSS) upstream of said ORF,
- wherein said one or more synthetic response elements and said core promoter increase transcription of said gene in said cancer cell of said subject as compared with a non-cancer cell.
A method comprising:
- administering a recombinant polynucleotide to a subject, wherein said recombinant polynucleotide comprises:
- a) one or more synthetic response elements comprising one or more enhancers and a plurality of transcription factor binding sites, wherein said one or more enhancers comprises a sequence having at least 80% sequence identity to at least one of:
- i. bases 1-11, 15-64, and 74-123 of SEQ ID NO:
- 386,
- ii. bases 1-15, 26-40, 51-65, 76-90, 101-115, and 126-140 of SEQ ID NO:
- 388, or
- iii. bases 1-14, 17-26, 29-37, 40-49, and 52-64 of SEQ ID NO:
- 384, or a reverse complement thereof;
- b) a core promoter operably linked to an open reading frame (ORF) comprising a gene, wherein said core promoter comprises a promoter element obtained from one or more cancer-responsive genes;
- and
- c) a transcription start site (TSS) upstream of said ORF.
A method comprising administering a recombinant polynucleotide to a subject, wherein said recombinant polynucleotide comprises:
- (a) a sequence that is at least 85% identical to bases 1-123, 136-275, 294-371, 378-443, and 455-581 of SEQ ID NO:
- 556 encoding a synthetic response sensor (SRS);
- and
- (b) an open reading frame (ORF) comprising a gene, wherein said ORF is operably linked to said SRS.
A method comprising administering a recombinant polynucleotide to a subject, wherein said recombinant polynucleotide comprises:
- (a) a sequence that is at least 85% identical to bases 1-123, 136-275, 294-371, 378-443, and 455-705 of SEQ ID NO:
- 557 encoding a synthetic response sensor (SRS);
- and
- (b) an open reading frame (ORF) comprising a gene, wherein said ORF is operably linked to said SRS.
Dependencies are inferred from the claim text.