The Johns Hopkins University

Ronald Rodriguez

Shawn Lupold

Wasim Haider Chowdhury

Tarana A Kudrolli

Ying Li

Ping Wu

Naser Uddin Hoti

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.

Compositions and methods for retargeting virus constructs

The present invention provides DNA libraries, libraries of viral clones and libraries of infectious viral particles and methods of generating and screening these libraries.

Compositions and methods for generating and screening adenoviral libraries

The present invention includes the use of a nucleic acid sequence encoding an shRNA to target RNA interference against a cellular factor where such use can enhance oncolytic adenovius replication. The nucleic acid sequence encoding an shRNA can be introduced into an oncolytic adenovius construct via a recombination event, and such nucleic acid sequence encoding an shRNA can reside in either the E1 region or Fiber region of the oncolytic adenovius construct. In particular, the oncolytic adenovius construct optionally include a prostate specific promoter or prostate specific enhancer for issue specific expression in prostate cancer cells. The oncolytic adenovius constructs of the invention provides utility for the treatment of cancers, in particular prostate cancer.

Compositions and methods for treatment of cancer using tissue-specific oncolytic adenoviruses

The instant invention provides methods and compositions for generating recombinant adenoviral vectors. The invention also provides kits comprising for the generation of recombinant adenoviral vectors.

Adenoviral fiber exchange shuttle system

The invention provides isolated PSMA binding peptides, as well as pharmaceutical compositions thereof. Also provided are diagnostic and therapeutic methods utilizing the PSMA binding peptides, as well as methods for identifying further PSMA binding peptides.

Peptides for targeting the prostate specific membrane antigen

The present invention relates to compositions and methods for enhancing the oncolytic activity of replication-competent, target cell-specific adenovirus vectors by modification of the E1A gene product. The target cell-specific replication-competent adenovirus vectors comprise a chimera of an adenovirus gene essential for replication, preferably an early gene, and the Androgen receptor (or a portion thereof) under the transcriptional control of a cell type-specific transcriptional regulatory element (TRE). By providing for cell type-specific transcription through the use of one or more cell type-specific TREs, the adenovirus vectors effect prostate-specific cytotoxicity due to selective replication.

Enhancement of adenoviral oncolytic activity by modification of the E1A gene product

The invention provides a packaging cell line for production of diphtheria toxin (DT) expressing, non-replicating adenovirus for use in suicide gene therapy of cancer cells, as well as production of immunotoxins. Also provided are methods for producing diphtheria toxin (DT) expressing, non-replicating adenovirus, methods for producing immunotoxins, and adenovirus and immunotoxins produced by those methods. Further provided are methods for making a cell resistant to diphtheria toxin.

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Glenwood, MD, United States of America

Ronald Rodriguez