Harvard College

The United States of America as Represented by the Department of Health

University of California

The United States of America

The United States of America as Represented by the Secretary of Health

Peter M Howley

John D Benson

Hiroyuki Sakai

Hiroaki Kasukawa

Martin Scheffner

Jon M Huibregtse

Jennifer J Dowhanick-Morrissette

Douglas Hanahan

Jeffrey M Arbeit

Jack H Lichy

Toshiharu Yasugi

Ming-Fan Law

Pengbo Zhou

Nava Sarver

By virtue of the present invention, there is provided methods and compositions for interfering with the proliferation of cells infected and/or transformed by papillomaviruses. The processes and compositions of this invention may be used to treat any mammal, including humans. According to this invention, mammals are treated by the pharmaceutically acceptable administration of an E2protein, either directly or by gene transfer techniques, to reduce the symptoms of the specific papillomavirus-associated disease, or to prevent their recurrence.

Compositions and methods for treating papillomavirus-infected cells

By virtue of the present invention, there is provided methods and compositions for interfering with the proliferation of cells infected and/or transformed by papillomaviruses. The processes and compositions of this invention may be used to treat any mammal, including humans. According to this invention, mammals are treated by the pharmaceutically acceptable administration of an E2 peptidomimetic to reduce the symptoms of the specific papillomavirus-associated disease, or to prevent their recurrence.

The present invention relates to methods and reagents for targeting proteolysis of a polypeptide by cis or trans association with a ubiquitin protein ligase, and further provides methods and reagents for inhibiting the ubiquitination and proteolysis of cellular proteins which are recognized by a ubiquitin protein ligase.

Targeted proteolysis by recruitment to ubiquitin protein ligases

By virtue of the present invention, there is provided methods and compositions for interfering with the proliferation of cells infected and/or transformed by papillomaviruses. The processes and compositions of this invention may be used to treat any mammal, including humans. According to this invention, mammals are treated by the pharmaceutically acceptable administration of an E2 protein, either directly or by gene transfer techniques, to reduce the symptoms of the specific papillomavirus-associated disease, or to prevent their recurrence.

Compositions and methods for treating Papillomavirus-infected cells

The present invention provides compositions of isolated and purified E6 Associated Protein and fragments thereof. Also provided are nucleic acid constructs encoding E6 Associated Protein. These compositions may be employed to identify compounds which inhibit binding of high risk HPV E6 to p53. The compositions of the present invention may also be used in methods to detect the presence of high risk HPV in biological samples.

E6 associated protein

Methods, kits, and compositions are provided for diagnosing papillomavirus infections by detecting the interaction between a papillomavirus E1 protein interaction domain and a papillomavirus E2 protein interaction domain.

Methods, kits, and compositions for diagnosing papillomavirus infection

The present invention relates to improved models for progressive epithelial neoplasias and methods for their use. In particular, the invention provides transgenic mice comprising a human papilloma virus early region oncogene operably linked to a promoter which directs expression of the oncogene in a transient amplifying cell in the mice.

Transgenic mice expressing HPV early region oncogene develop progressive

E6 associated protein and methods of use thereof

A gene which is associated with tumor suppression and is localized on chromosome 11 has now been identified. The identification, localization and sequence of a gene which demonstrates differential expression in a manner that correlates with tumorigenicity suggests that this gene could potentially be used for gene therapy in cancers deleted or altered in their expression of the gene. Furthermore, a gene which is localized on chromosome 11p15, with identified polymorphisms, could be used for analysis of tumor DNA for loss of heterozygosity at chromosome 11p15. This region of chromosome 11 shows frequent loss of heterozygosity (LOH) in many human malignancies. Thus, the determination of LOH at chromosome 11p15 may be useful in predicting the prognosis of that tumor.

HTS-1 gene, a human tumor suppressor gene

A novel method and composition are provided for the replication and expression of exogenous genes in eukaryotic cells. A segment of a papilloma virus genome capable of extrachromosomal replication is linked to the foreign gene(s) using recombinant DNA techniques to provide a biologically functional replicon with a desired phenotypical property. The replicon is inserted into a eukaryotic cell by transformation, and the isolation of transformant provides cells for replication and expression of the DNA molecules present in the modified plasmid. The transforming region of the bovine papilloma virus provides a unique vector in that it provides both the capability of autonomous extrachromosomal replication but also the malignant transformed phenotype. Thus, genes which of themselves provide no selectable phenotypical property can be conveniently and efficiently introduced into eukaryotic cells and the transformants selected. The method is useful in that the foreign DNA is faithfully expressed and the gene products (proteins), such as pro-insulin (an insulin precursor) is synthesized.

Growing community of inventors

Wellesley, MA, United States of America

Peter M Howley