The Penn State Research Foundation

Other

Medical University of South Carolina

Musc Foundation for Research Development

Clawnor, Inc.

Gary A Clawson

Wei-Hua Pan

Brian Hoel

James S Norris

Michael G Schmidt

David P Schofield

Joseph W Dolan

Caroline Westwater

James W Norris

Michael James Schmidt

Neil D Christensen

Craig M Meyers

Joseph F Dolan

Diane Thiboutot

David Drubin

Molly McLaughlin-Drubin

The present invention relates to multi-ribozymes and their use to target RNA in a tissue-specific, target RNA-specific, or pathogen-specific manner for the treatment of cancers, proliferative disease, and bacterial, parasitic and viral infections. More specifically, the present invention relates to the use of virions and viral vectors to package and deliver DNA encoding the multi-ribozymes to a host. The present invention relates to the use of liposomes and lipid-DNA complexes to deliver DNA encoding ribozymes to a host. Most specifically, the invention relates to the use of target specific virions to package and deliver DNA comprising a target specific promoter and encoding a ribozyme(s) directed to the target organism nucleic acids. The present invention further relates to a novel vectors encoding a multi-ribozyme structure with enhanced 5' and/or 3&#x2032; autocatalytically cleaving ribozymes. The invention further relates to nucleotides encoding a multi-ribozyme comprising one or more ribozyme cassettes which contain one or more trans-acting ribozymes and one or more autocatalytically cleaving ribozyme sequences.

Tissue-specific and target RNA-specific ribozymes

The invention provides methods and materials related to treating HPV infections (e.g., HPV infections of cutaneous and mucosal epithelial cells) and HPV-associated conditions (e.g., cervical dysplasia, HPV-associated cervical carcinomas, oral mucosal papilloma cancers, laryngeal papilloma cancers).

Methods and materials for treating human papillomavirus infections

The present invention relates to the discovery, identification and characterization of toxic agents which are lethal to pathogens and methods for targeting such toxic agents to a pathogen or pathogen infected cells in order to treat and/or eradicate the infection. In particular, the present invention relates to toxic agents which target bacteria at different stages of the bacterial life cycle, which are delivered alone or in combination to bacteria or bacteria-infected cells. The invention relates to toxic agents which are lethal to diseased cells and methods for targeting such toxic agents to a diseased cell in order to treat and/or eradicate the disease. The present invention relates to promoter elements which are pathogen-specific or tissue-specific and the use of such promoter elements to achieve pathogen-specific or tissue-specific expression of the toxic agent(s) and/or ribozyme(s) of the present invention. Specifically, the invention relates to the delivery of one or more toxic gene products, antisense RNAs, or ribozymes, or combination thereof. The invention provides a novel system by which multiple pathogenic targets may be simultaneously targeted to cause the death of a pathogen, or cell infected with a pathogen. Further, the invention has important implications in the eradication of drug-resistant bacterium and bacterial pathogens. The invention provides a novel system by which multiple targets may be simultaneously targeted to cause the death of a diseased cell. The invention has important implications in the eradication of drug-resistant pathogens (such as antibiotic resistant bacteria) and drug-resistant diseased cells (such as drug-resistant cancer cells).

Tissue-specific and pathogen-specific ribozymes

In the US about &#x2153; of college women show evidence of HPV infection. The clinical problem may be even larger in developing countries. There are currently no effective therapies for HPV infections, aside from therapeutic cone biopsies, which often are followed by recurrent, progressive lesions. Thus, pharmaceutical compositions and processes for treatment of an HPV infection are detailed. In particular, a pharmaceutical composition for inhibiting growth of a human papilloma virus-infected cell is provided which includes a peptide halomethyl ketone inhibitor of a chymotrypsin or chymotrypsin-like protease and a pharmaceutically acceptable carrier. A preferred inhibitor is AAPFcmk.

Compositions and methods for inhibiting abnormal cell growth

The present invention relates to the discovery, identification and characterization of toxic agents which are lethal to pathogens and methods for targeting such toxic agents to a pathogen or pathogen infected cells in order to treat and/or eradicate the infection. In particular, the present invention relates to toxic agents which target bacteria at different stages of the bacterial life cycle, which are delivered alone or in combination to bacteria or bacteria-infected cells. The invention relates to toxic agents which are lethal to diseased cells and methods for targeting such toxic agents to a diseased cell in order to treat and/or eradicate the disease. The present invention relates to promoter elements which are pathogen-specific or tissue-specific and the use of such promoter elements to achieve pathogen-specific or tissue-specific expression of the toxic agent(s) and/or ribozyme(s) of the present invention. Specifically, the invention relates to the delivery of one or more toxic gene products, antisense RNAs, or ribozymes, or combination thereof. The invention provides a novel system by which multiple pathogenic targets may be simultaneously targeted to cause the death of a pathogen, or cell infected with a pathogen. Further, the invention has important implications in the eradication of drug-resistant bacterium and bacterial pathogens. The invention provides a novel system by which multiple targets may be simultaneously targeted to cause the death of a diseased cell. The invention also has important implications in the eradication of drug-resistant pathogens and drug-resistant diseased cells (such as cancer cells).

Tissue-specific and pathogen-specific toxic agents and ribozymes

The invention provides tissue-specific and target RNA-specific ribozymes. These ribozymes can be used to destroy target-specific neoplasms and to treat viral infections, among other uses. The ribozymes of the present invention comprise a 5' autocatalytically cleaving ribozyme sequence, a catalytic ribozyme comprising a target RNA-specific binding site and a 3' autocatalytically cleaving ribozyme. The invention also provides nucleic acids which encode the ribozymes of the invention. These nucleic acids can be used to express the ribozymes of the invention at the selected site. Methods of treating disease by administering the ribozymes are provided.

Growing community of inventors

Bethesda, MD, United States of America

Gary A Clawson