The State University of New York

Codagenix, Inc.

National Institutes of Health, a Component of the US Dept. of Health & Human Services

United States of America, As Represented by the Secretary of Agriculture

The Usa, Secretary, Dhhs

Steffen Mueller

Eckard Wimmer

Peter L Collins

Ursula J Buchholz

Bruce Futcher

John Robert Coleman

Jeronimo Cello

Steve Skiena

Linda G Brock

Dimitris Papamichail

Joshua Marc DiNapoli

Steven S Skiena

Cyril Le Nouën

Cyril Lenouen

Chen Yang

Ying Wang

Aida Elizabeth Rieder

Charles D Ward

Teresa B De Los Santos

Fayna C Diaz-San Segundo

Sam Shen

Charles Stauft

Anna Kloc

Gisselle N Medina

Steven Skiena

The present invention is the use of designed recombinant viruses for the treatment of various forms of malignant tumors. The recombinant viruses of the invention are those in which one or more regions of the wild type virus was exchanged with a synthetic recoded sequence that reduces the codon pair score relative to human codon pair bias, or that increase the number for CpG di-nucleotides, or that increases the number of UpA di-nucleotides. The method of the present invention is particularly useful for the treatment of malignant tumors in various organs, such as: breast, skin, 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, as well as for the treatment of breast cancer and melanoma as well.

Recombinant virus with codon-pair deoptimized region and uses thereof for the treatment of cancer

The present invention provides for modified Flavivirus such as a modified Zika virus. The modification according to various aspects of the invention results in reduced viral proteins compared to a parent virus, wherein the reduction in expression is the result of recoding one or more regions of the virus. For example, the prM, or envelope (E) region, or the nonstructural protein 3 (NS3) region or both the E and NS3 regions can be recoded. In various embodiments one or more regions are recoded by reducing the codon pair bias or codon usage bias of the protein-encoding sequence. These modified Flavivirus are used as vaccine compositions to provide a protective immune response.

Attenuated flaviviruses

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

Reported herein are presumptively de-attenuating mutations that are useful, either individually or in combinations that may include other known mutations, in producing recombinant strains of human respiratory syncytial virus (RSV) exhibiting attenuation phenotypes. Also described herein is a novel RSV construct, Min_L-NPM2-1(N88K)L, which exhibits an attenuated phenotype, is stable and is as immunogenic as wild type RSV. The recombinant RSV strains described here are suitable for use as live-attenuated RSV vaccines. Exemplary vaccine candidates are described. Also provided are polynucleotide sequences capable of encoding the described viruses, as well as methods for producing and using the viruses.

Vaccine candidates for human respiratory syncytial virus (RSV) having attenuated phenotypes

The present disclosure describes deoptimized foot and mouth viruses and their use for prophylactic and therapeutic treatment of mammalian subjects. The recombinant viruses provided herein include alterations in several genomic regions as well as Differentiating Infected from Vaccinated Animals (DIVA) markers.

Live attenuated strains of foot and mouth disease modified by deoptimization and uses thereof

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

Growing community of inventors

Kings Point, NY, United States of America

Steffen Mueller