Compositions and methods for retargeting virus constructs

Patent metadata

Field	Value
Publication number	US-9458473-B2
Application number	US-201113807359-A
Country	US
Kind code	B2
Filing date	Jun 29, 2011
Priority date	Jun 29, 2010
Publication date	Oct 4, 2016
Grant date	Oct 4, 2016

Abstract

The present invention relates to the field of viral gene therapy. More specifically, the present invention provides compositions and methods for retargeting virus constructs. In one embodiment, the present invention provides an adenoviral construct comprising a nucleic acid encoding the peptide sequence MAE-X-PDP (SEQ ID NO:45), wherein X is an antigen targeting peptide. In a more specific embodiment, an adenoviral construct comprises a nucleic acid sequence encoding the peptide sequence MAEWQPDTAHHWALTLPDP (SEQ ID NO:10) inserted into the HI-loop of adenovirus fiber protein. In yet another embodiment, the present invention provides a method for optimizing adenoviral infection of target cells comprising the steps of (a) generating a peptide-display adenovirus library, wherein the displayed peptide is a peptide that specifically binds an antigen expressed on the surface of a target cell, and wherein the displayed peptide is flanked by random peptide sequences; and (b) screening the peptide-display adenovirus library against the target cells.

First claim

We claim:

1. A method for optimizing infection of target cells by an adenovirus displaying an antigen targeting peptide comprising the steps of:
a. selecting an antigen targeting peptide to be displayed in an adenovirus, wherein the displayed targeting peptide is a peptide that specifically binds an antigen expressed on the surface of a target cell;
b. generating peptide-display adenovirus library that displays the selected antigen targeting peptide of step (a), wherein the amino acid sequence encoding the displayed antigen targeting peptide is flanked by random peptide sequences; and
c. screening the antigen targeting peptide-display adenovirus library against the target cells to isolate adenovirus that optimally infects the target cells.

2. The method of claim 1 , wherein one or both of the flanking random peptide sequences are selected from the group consisting of a monomer, a dimer, a trimer, a tetramer, a pentamer, a hexamer, a septamer, a octamer, and a nonamer.

3. The method of claim 1 , wherein the flanking random peptide sequences are multimers.

4. The method of claim 1 , wherein the flanking random peptide sequences are trimers.

5. The method of claim 1 , wherein the target cell is a cancer cell.

Assignees

• Lupold Shawn Edward
• Wu Ping
• Rodriguez Ronald
• Univ Johns Hopkins

Inventors

• Lupold Shawn Edward
• Wu Ping
• Rodriguez Ronald

Classifications

• C12N15/1037

  Screening libraries presented on the surface of microorganisms, e.g. phage display, E. coli display · CPC title

• C12N2710/10322

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title

• C12N2710/10345

  Special targeting system for viral vectors · CPC title

• C12N2820/007

  tissue or cell-specific · CPC title

• A61P35/00

  Antineoplastic agents · CPC title