Multiple inducible gene regulation system

1. A multiple inducible gene modulation system consisting of two individually operable heterologous gene modulation systems,

wherein each individually operable heterologous gene modulation system comprises:

a) a first gene expression cassette comprising a polynucleotide sequence that encodes a polypeptide comprising:

A) a DNA binding domain that recognizes a response element associated with a gene of interest;

B) an ecdysone receptor ligand binding domain; and

b) a second gene expression cassette comprising a polynucleotide sequence comprising a promoter operably linked to a polynucleotide sequence that encodes a second polypeptide comprising a nuclear receptor ligand binding domain and a transactivation domain; and

wherein each individually operable heterologous gene modulation system is orthogonal to the other individually operable heterologous gene modulation system present in the multiple inducible gene modulation system.

2. A virus comprising the multiple inducible gene regulation system of claim 1 .

3. An isolated cell comprising the multiple inducible gene regulation system of claim 1 .

4. The multiple inducible gene modulation system of claim 1 , wherein said nuclear receptor ligand binding domain is selected from the group consisting of a vertebrate retinoid X receptor ligand binding domain; an invertebrate retinoid X receptor ligand binding domain; an ultraspiracle protein ligand binding domain; and a chimeric ligand binding domain comprising two polypeptide fragments, wherein the first polypeptide fragment is from a vertebrate retinoid X receptor ligand binding domain, an invertebrate retinoid X receptor ligand binding domain, or an ultraspiracle protein ligand binding domain, and the second polypeptide fragment is from a different vertebrate retinoid X receptor ligand binding domain, invertebrate retinoid X receptor ligand binding domain, or an ultraspiracle protein ligand binding domain.

5. The multiple inducible gene modulation system of claim 1 , wherein said ecdysone receptor ligand binding domain is selected from the group consisting of a Lepidopteran ecdysone receptor ligand binding domain, a Dipteran ecdysone receptor ligand binding domain, an Arthropod ecdysone receptor ligand binding domain, an Orthopteran ecdysone receptor ligand binding domain, a Homopteran ecdysone receptor ligand binding domain, a Hemipteran ecdysone receptor ligand binding domain, a spruce budworm Choristoneura fumiferana ecdysone receptor ligand binding domain, a yellow meal worm Tenebrio molitor ecdysone receptor ligand binding domain, a tobacco hornworm Manduca sexta ecdysone receptor ligand binding domain, a tobacco budworm Heliothies virescens ecdysone receptor ligand binding domain, a golmidge Chironomus tentans ecdysone receptor ligand binding domain, a silkworm Bombyx mori ecdysone receptor ligand binding domain, a squinting bush brown Bicyclus anynana ecdysone receptor ligand binding domain, a buckeye Junonia coenia ecdysone receptor ligand binding domain, a fruit fly Drosophila melanogaster ecdysone receptor ligand binding domain, a yellow fever mosquito Aedes aegypti ecdysone receptor ligand binding domain, a blowfly Lucilia capitata ecdysone receptor ligand binding domain, a sheep blowfly Lucilia cuprina ecdysone receptor ligand binding domain, a blowfly Calliphora vicinia ecdysone receptor ligand binding domain, a Mediterranean fruit fly Ceratitis capitata ecdysone receptor ligand binding domain, a locust Locusta migratoria ecdysone receptor ligand binding domain, an aphid Myzus persicae ecdysone receptor ligand binding domain, a fiddler crab Celuca pugilator ecdysone receptor ligand binding domain, an ixodid tick Amblyomma americanum ecdysone receptor ligand binding domain, and a white fly Bamecia argentifoli ecdysone receptor ligand binding domain.

6. The multiple inducible gene modulation system of claim 5 , wherein said ecdysone receptor ligand binding domain is a spruce budworm Choristoneura fumiferana ecdysone receptor ligand binding domain.

7. The multiple inducible gene modulation system of claim 1 , wherein said DNA binding domain is selected from the group consisting of a GAL4 DNA binding domain, a LexA DNA binding domain, a transcription factor DNA binding domain, a Group H nuclear receptor member DNA binding domain, a steroid/thyroid hormone nuclear receptor superfamily member DNA binding domain, a bacterial LacZ DNA binding domain, and an ecdysone receptor DNA binding domain.

8. The multiple inducible gene modulation system of claim 1 , wherein said transactivation domain is selected from the group consisting of a Group H nuclear receptor member transactivation domain, a steroid/thyroid hormone nuclear receptor transactivation domain, a polyglutamine transactivation domain, a basic or acidic amino acid transactivation domain, a VP16 transactivation domain, a GAL4 transactivation domain, an NF-KB transactivation domain, a BP64 transactivation domain, a B42 acidic transactivation domain, and a p65 transactivation domain.

9. The virus of claim 2 , wherein said virus is an adenovirus.

10. A vector comprising the multiple inducible gene modulation system of claim 1 .

11. The vector of claim 10 , wherein said vector is a plasmid.

12. The vector of claim 10 , wherein said vector is an expression vector.

13. The vector of claim 10 , wherein said vector is a viral vector.

14. The vector of claim 13 , wherein said vector is an adenovirus vector.

15. The isolated cell of claim 3 , wherein said cell is selected from the group consisting of a bacterial cell, a fungal cell, a yeast cell, an animal cell and a mammalian cell.

16. The isolated cell of claim 15 , wherein said cell is a mammalian cell.

17. The isolated cell of claim 15 , wherein said mammalian cell is selected from the group consisting of a hamster cell, a murine cell, a monkey cell, a mouse cell, a rat cell, a rabbit cell, a cat cell, a dog cell, a bovine cell, a goat cell, a pig cell, a horse cell, a sheep cell, a monkey cell, a chimpanzee cell and a human cell.

18. The isolated cell of claim 17 , wherein said mammalian cell a human cell.

19. The multiple inducible gene modulation system of claim 1 , wherein each individually operable heterologous gene modulation system is associated with an expression cassette comprising a response element to which the DNA-binding domain binds, a promoter that is activated by the transactivation domain, and a gene of interest.