Desmoglein 2 (DSG2) binding proteins and uses therefor

1. A recombinant AdB-2/3 fiber polypeptide, comprising:

(a) one or more AdB-2/3 fiber polypeptide shaft domain motifs;

(b) an AdB-2/3 fiber polypeptide knob domain operatively linked to and located C-terminal to the one or more AdB-2/3 fiber polypeptide shaft domain motifs, wherein the AdB-2/3 fiber polypeptide knob domain comprises the peptide of SEQ ID NO:4 TLWTGPKPEA NCIIEYGKQN PDSKLTLILV KNGG(I/L)VNGYV TLMGASDYVN TLFKNKNVSI NVELYFDATG HILPDSSSLK TDLEX2 X3YKQTAD X4 SARGFMP STTAYPFX5LP NAGTHNX6NX7 IFGQCYY X8 ASDGALFPLEVTV MLNKRLPDSR TSYVMTFLWS LX9AGLAPETT QATLITSPFT FSYIREDD (SEQ ID NO:4),

wherein:

X2 is H, L, or P;

X3 is K or E;

X4 is T, F, S, or L;

X5 is V, or D;

X6 is E or G;

X7 is Y or F;

X8 is T, K, or E; and

X9 is N or S; and

wherein at least one of the following is true:

X2 is P;

X3 is E;

X4 is S, or L;

X5 is D;

X6 is G;

X7 is F;

X8 is E; or

X9 is S; and

(c) one or more non-AdB-2/3-derived dimerization domains operatively linked to and located N-terminal to the one or more AdB-2/3 fiber polypeptide shaft domain motifs.

2. The recombinant AdB-2/3 fiber polypeptide of claim 1 , wherein the AdB-2/3 fiber polypeptide does not include an AdB-2/3 fiber polypeptide tail domain.

3. The recombinant AdB-2/3 fiber polypeptide of claim 1 , wherein each shaft domain motif is selected from the group consisting of an Ad3 fiber polypeptide shaft domain motif, an Ad7 fiber polypeptide shaft domain motif, an Ad11 fiber polypeptide shaft domain motif, an Ad14 fiber polypeptide shaft domain motif, an Ad14a fiber polypeptide shaft domain motif, and combinations thereof.

4. The recombinant AdB-2/3 fiber polypeptide of claim 1 , wherein the one or more shaft domain motifs comprise 1-22 shaft domain motifs.

5. The recombinant AdB-2/3 fiber polypeptide of claim 1 , wherein each shaft domain motif comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 43-48.

6. The recombinant AdB-2/3 fiber polypeptide of claim 1 , wherein the dimerization domain comprises an amino acid sequence selected from the group consisting of EVSALEK (SEQ ID NO:24) and/or KVSALKE (SEQ ID NO: 25).

7. The recombinant AdB-2/3 fiber polypeptide of claim 1 , wherein the one or more shaft domain motifs are the shaft domain motif of SEQ ID NO:43.

8. The recombinant AdB-2/3 fiber polypeptide of claim 1 , comprising the amino acid sequence of

(a)

(SEQ ID NO: 28)

(M/)GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGGG

SGGGSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIVN

GYVTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLELKY

KQTADFSARGFMPSTTAYPFVLPNAGTHNENFIFGQCYYKASDGALFPLE

VTVMLNKRLPDSRTSYVMTFLWSLNAGLAPETTQATLITSPFTFSYIRED

D;

(b)

(SEQ ID NO: 29)

(M/)GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGGG

SGGGSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIVN

GYVTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLELEY

KQTADSSARGFMPSTTAYPFVLPNAGTHNENYIFGQCYYKASDGALFPLE

VTVMLNKRLPDSRTSYVMTFLWSLNAGLAPETTQATLITSPFTFSYIRED

D;

(c)

(SEQ ID NO: 30)

(M/-)GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGG

GSGGGSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIV

NGYVTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLELK

YKQTADFSARGFMPSTTAYPFVLPNAGTHNENYIFGQCYYKASDGALFPL

EVTVMLNKRLPDSRTSYVMTFLWSLSAGLAPETTQATLITSPFTFSYIRE

DD;

(d)

(SEQ ID NO: 31)

(M/-)GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGG

GSGGGSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIV

NGYVTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLELK

YKQTADFSARGFMPSTTAYPFDLPNAGTHNENYIFGQCYYKASDGALFPL

EVTVMLNKRLPDSRTSYVMTFLWSLNAGLAPETTQATLITSPFTFSYIRE

DD;

(e)

(SEQ ID NO: 32)

(M/-)GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGG

GSGGGSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIL

VNGYVTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLEP

KYKQTADFSARGFMPSTTAYPFVLPNAGTHNENYIFGQCYYFASDGALFP

LEVTVMLNKRLPDSRTSYVMTFLWSLNAGLAPETTQATLITSPFTFSYIR

EDD;

(F)

(SEQ ID NO: 33)

(M/-)GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGG

GSGGGSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIV

NGYVTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLELK

YKQTADLSARGFMPSTTAYPFVLPNAGTHNENYIFGQCYYKASDGALFPL

EVTVMLNKRLPDSRTSYVMTFLWSLNAGLAPETTQATLITSPFTFSYIRE

DD; 

and/or

(g)

(SEQ ID NO: 34)

(M/-)GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGG

GSGGGSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIV

NGYVTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLELK

YKQTADFSARGFMPSTTAYPFVLPNAGTHNGNYIFGQCYYEASDGALFPL

EVTVMLNKRLPDSRTSYVMTFLWSLNAGLAPETTQATLITSPFTFSYIRE

DD.

9. The recombinant AdB-2/3 fiber polypeptide of claim 1 , wherein the AdB-2/3 fiber polypeptide contains a single AdB-2/3 fiber polypeptide shaft domain motif.

10. The recombinant AdB-2/3 fiber polypeptide of claim 1 , wherein the AdB-2/3 fiber polypeptide is multimerized.

11. The recombinant AdB-2/3 fiber polypeptide of claim 1 , wherein the AdB-2/3 fiber polypeptide is dimerized.

12. The recombinant AdB-2/3 fiber polypeptide of claim 1 , further comprising one or more compounds conjugated to the recombinant AdB-2/3 fiber polypeptide.

13. The recombinant AdB-2/3 fiber polypeptide of claim 12 , wherein the one or more compounds are selected from the group consisting of therapeutics, diagnostics, and imaging agents.

14. The recombinant AdB-2/3 fiber polypeptide of claim 13 , wherein the one or more compounds comprise at least one therapeutic, wherein the therapeutic is selected from the group consisting of antibodies, immunoconjugates, nanoparticles, chemotherapeutics, radioactive particles, viruses, vaccines, cellular immunotherapy therapeutics, gene therapy constructs, nucleic acid therapeutics, and combinations thereof.

15. An isolated nucleic acid encoding the recombinant AdB-2/3 fiber polypeptide of claim 1 .

16. A recombinant expression vector comprising the isolated nucleic acid of claim 15 .

17. An isolated host cell comprising the recombinant expression vector of claim 16 .

18. A pharmaceutical composition, comprising

(a) the AdB-2/3 fiber multimer of claim 10 ; and

(b) a pharmaceutically acceptable carrier.

19. A method for enhancing therapeutic treatment, or diagnosis of a disorder associated with epithelial tissue, and/or imaging epithelial tissues, comprising administering to a subject in need thereof:

(a) an amount of one or more therapeutics sufficient to treat the disorder, diagnostic sufficient to diagnose the disorder, and/or imaging agent sufficient to image the epithelial tissue; and

(b) an amount of the AdB-2/3 fiber multimer of claim 10 sufficient to enhance efficacy of the one or more therapeutics, diagnostics, and/or imaging agents.

20. A method for treating a disorder associated with epithelial tissue, comprising administering to a subject in need thereof an amount of the AdB-2/3 fiber multimer of claim 10 sufficient to treat the disorder.

21. A method for improving delivery of a compound to an epithelial tissue, comprising contacting the epithelial tissue with

(a) one or more compounds to be delivered to the epithelial tissue; and

(b) an amount of the AdB-2/3 fiber multimer of claim 10 sufficient to enhance delivery of the one or more compounds to the epithelial tissue.

22. A method for improving delivery of a substance to a tissue expressing desmoglein 2 (DSG2), comprising contacting the tissue expressing DSG2 with

(a) one or more compound to be delivered to the tissue; and

(b) an amount of the AdB-2/3 fiber multimer of claim 10 sufficient to enhance delivery of the one or more compounds to the tissue.

23. A method for inducing an epithelial to mesenchymal transition (EMT) in a tissue, comprising contacting the epithelial tissue with an amount of the AdB-2/3 fiber multimer of claim 10 sufficient to induce EMT.

24. The recombinant AdB-2/3 fiber polypeptide of claim 1 , wherein the AdB-2/3 fiber polypeptide knob domain comprises the peptide selected from the group consisting of SEQ ID NOS: 5-11.

25. The recombinant AdB-2/3 fiber polypeptide of claim 1 , wherein the AdB-2/3 fiber polypeptide knob domain comprises the peptide of SEQ ID NO:8.

26. The recombinant AdB-2/3 fiber polypeptide of claim 25 , wherein the AdB-2/3 fiber polypeptide is multimerized.

27. The recombinant AdB-2/3 fiber polypeptide of claim 25 , further comprising one or more compounds conjugated to the recombinant AdB-2/3 fiber polypeptide, wherein the one or more compounds are selected from the group consisting of therapeutics, diagnostics, and imaging agents.

28. A pharmaceutical composition, comprising

(a) the AdB-2/3 fiber polypeptide multimer of claim 26 ; and

(b) a pharmaceutically acceptable carrier.