Adenovirus library and methods
Described herein is a method that generally includes infecting a host cell with a rescue adenovirus, wherein the rescue adenovirus genome comprises a loxP site and encodes at least one marker, and wherein the host cell comprises a library of polynucleotides that complement the adenovirus genome marker and encode a detectable polypeptide; incubating the infected host cell under conditions effective to permit recombination between the adenovirus genome and one or more of the library polynucleotides and the production of recombinant adenovirus particles comprising at least on detectable polypeptide; and detecting the at least one detectable polypeptide. Also described are adenovirus libraries constructed using such a method.
1. An adenovirus comprising:
an AB loop comprising a targeting peptide, the targeting peptide comprising the amino acid sequence VTINRSA (SEQ ID NO:12).
2. A method comprising:
contacting the adenovirus of claim 1 with a target cell that expresses mesothelin;
allowing the adenovirus to bind to mesothelin expressed by the target cell; and
allowing the adenovirus to infect the target cell.
3. The method of claim 2 , wherein the target cell is a tumor cell.
4. The method of claim 3 , wherein the tumor cell is a pancreatic tumor cell.
5. The method of claim 3 , wherein the tumor cell is a lung carcinoma cell.
6. The method of claim 2 , wherein the adenovirus is contacted with the target cell in vivo.
7. The method of claim 6 , wherein the adenovirus is administered systemically to a subject harboring the target cell.
8. A method for targeted delivery of anti-tumor therapy to a subject, the method comprising:
administering to the subject the adenovirus of claim 1 ;
allowing the adenovirus to bind to a tumor cell that expresses mesothelin;
allowing the adenovirus to infect the tumor cell, thereby delivering anti-tumor therapy.
9. The method of claim 8 , wherein the anti-tumor therapy comprises:
replication of the adenovirus; and
lysis of the tumor cell.
10. The method of claim 8 , wherein the anti-tumor therapy comprises:
delivery of a therapeutic polynucleotide; and
allowing the tumor cell to express the therapeutic polynucleotide.
11. The method of claim 8 , wherein the tumor cell is a pancreatic tumor cell.
12. The method of claim 8 , wherein the tumor cell is a lung carcinoma cell.
13. The method of claim 8 , wherein the adenovirus is administered to the subject systemically.