The State University of New York

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Mueller, Steffen

Wimmer, Eckard

Eckard Wimmer

Steffen Mueller

Bruce Futcher

Jeronimo Cello

Matthias Gromeier

Aniko V Paul

Peter L Collins

Ursula J Buchholz

John Robert Coleman

Steve Skiena

Cyril Le Nouën

Linda G Brock

Dimitris Papamichail

Joshua Marc DiNapoli

Steven S Skiena

Hidemi Toyoda

Jiang Yin

Chen Yang

Charles D Ward

Chengyu Liang

Sung Key Jang

Bumsuk Hahm

Elizabeth Rieder

Akhteruzzaman Molla

Sam Shen

Charles Stauft

Steven Skiena

Joshua Marc Dinapoli

Described herein are RSV polynucleotide sequences that make use of multiple codons that are containing silent nucleotide substitutions engineered in multiple locations in the genome, wherein the substitutions introduce a numerous synonymous codons into the genome. Due to the large number of defects involved, the attenuated viruses disclosed herein provide a means of producing attenuated, live vaccines against RSV.

Attenuation of human respiratory syncytial virus by genome scale codon-pair deoptimization

This invention provides highly attenuated influenza viruses and vaccines. The attenuated viruses and vaccines proliferate well and have high safety factors. The attenuated viruses providing protective immunity from challenge by virus of the same subtype, as well as cross protection against heterologous viruses.

Attenuated influenza viruses and vaccines

This invention provides an attenuated virus which comprises a modified viral genome containing nucleotide substitutions engineered in multiple locations in the genome, wherein the substitutions introduce synonymous deoptimized codons into the genome. The instant attenuated virus may be used in a vaccine composition for inducing a protective immune response in a subject. The invention also provides a method of synthesizing the instant attenuated virus. Further, this invention further provides a method for preventing a subject from becoming afflicted with a virus-associated disease comprising administering to the subject a prophylactically effective dose of a vaccine composition comprising the instant attenuated virus.

Attenuated viruses useful for vaccines

This invention provides an attenuated virus comprising a modified viral genome engineered to containing multiple nucleotide substitutions that reduce the codon pair bias of a virus protein encoding sequence relative to a first host while the codon pair bias relative to a second host is not substantially reduced. In another embodiment, the invention provides an attenuated virus comprising modified viral genome engineered to containing multiple nucleotide substitutions that reduce the codon pair bias of a virus protein-encoding sequence relative to a first host and a second host. The attenuated virus may be used in a vaccine composition for inducing a protective immune response in a subject. The invention also provides a method of synthesizing the attenuated virus. Further, this invention further provides a method for preventing a subject from becoming afflicted with a virus-associated disease comprising administering to the subject a prophylactically effective dose of a vaccine composition comprising the attenuated virus.

Attenuated virus having multiple hosts

Methods of making modified viral genomes

A novel and stable attenuated poliovirus, which replicates in neuroblastoma cells, is produced by engineering an indigenous replication element (cre), into the 5' non-translated genomic region and inactivating the native cre element located in the coding region of 2C (mono-crePV). The stably attenuated poliovirus replicates in a neuroblastoma model (Neuro-2atumors) expressing CD155, the poliovirus receptor, and is effective for oncolytic treatment and cure of solid tumors, such as neuroblastoma.

Attenuated poliovirus

The present invention is directed to non-pathogenic, oncolytic, recombinant polioviruses for the treatment of various forms of malignant tumors. The recombinant polioviruses of the invention are those in which the internal ribosomal entry site (IRES) of the wild type poliovirus was exchanged with the IRES of other picornaviruses, and optionally P1, P3 or the 3'NTR thereof was exchanged with that of poliovirus Sabin type. More particularly, the present invention is directed to the administration of the non-pathogenic, oncolytic, recombinant poliovirus to the tumor directly, intrathecally or intravenously to cause tumor necrosis. The method of the present invention is particularly useful for the treatment of malignant tumors in various organs, such as: breast, colon, bronchial passage, epithelial lining of the gastrointestinal, upper respiratory and genito-urinary tracts, liver, prostate and the brain. Astounding remissions in experimental animals have been demonstrated for the treatment of malignant glioblastoma multiforme, an almost universally fatal neoplasm of the central nervous system.

Recombinant poliovirus for the treatment of cancer

The present invention provides a Hepatitis C Virus (HCV) replicon that efficiently replicates in an eukaryotic cell. The HCV replicon includes a nucleic acid sequence encoding a subgenomic fragments of HCV of any genotype that confer on the RNA the ability to replicate, and a nucleic acid sequence encoding an acetyl transferase selectable marker, such as puromycin. Also provided is an HCV type 1a replicon that efficiently replicates in an eukaryotic cell and includes a nucleic acid sequence encoding subgenomic fragments of type 1a HCV that confer on the RNA the ability to replicate, and a nucleic acid sequence encoding a acetyl transferase selectable marker. Further provided are eukaryotic cell lines that include an HCV replicon or an HCV type 1a replicon which efficiently replicate in the eukaryotic cell. The present invention also provides screening methods for identifying candidate compounds that inhibit the propagation of HCV.

Efficient hepatitis C virus replicon and its use in identifying antiviral compounds

The present invention relates to a method of diagnosing, classifying and grading of tumor growths and to determine whether the use of chimeric polioviruses is a proper course for the treatment of the tumors. More particularly, the method is directed to the use of antibodies to a poliovirus receptor (PVR), CD155, to detect the presence of CD155 on tumor cells in various organs, such as: breast, colon, bronchial passage, epithelial lining of the gastrointestinal, upper respiratory and genito-urinary tracts, liver, prostate and the brain.

Method of detecting the presence of CD155 for diagnosis of cancer and to determine treatment

The present invention is directed to non-pathogenic, oncolytic, recombinant polioviruses for the treatment of various forms of malignant tumors. The recombinant polioviruses of the invention are those in which the internal ribosomal entry site (IRES) of the wild type poliovirus was exchanged with the IRES of other picornaviruses, and optionally P1, P3 or the 3&prime;NTR thereof was exchanged with that of poliovirus Sabin type. More particularly, the present invention is directed to the administration of the non-pathogenic, oncolytic, recombinant poliovirus to the tumor directly, intrathecally or intravenously to cause tumor necrosis. The method of the present invention is particularly useful for the treatment of malignant tumors in various organs, such as: breast, colon, bronchial passage, epithelial lining of the gastrointestinal, upper respiratory and genito-urinary tracts, liver, prostate and the brain. Astounding remissions in experimental animals have been demonstrated for the treatment of malignant glioblastoma multiforme, an almost universally fatal neoplasm of the central nervous system.

Growing community of inventors

East Setauket, NY, United States of America

Eckard Wimmer