Abstract: The present invention provides for modified Flavivirus such as a modified dengue virus type 1, 2, 3, 4, a combination of these, or a tetravalent combination of these. The modification according to various aspects of the invention results in reduced viral protein expression 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 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 Flaviviruses are used as vaccine compositions to provide a protective immune response.

Abstract: The present invention is the use of designed recombinant viruses for the treatment of various forms of malignant tumors using attenuated Yellow Fever virus. 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 treatment of breast cancer and melanoma.

Abstract: 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.

Abstract: 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.

Abstract: 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.