title: Downregulating viral gene expression: codon usage bias manipulation for the generation of novel influenza A virus vaccines.
abstract: Vaccination represents the best option to protect humans against influenza virus. However, improving the effectiveness of current vaccines could better stifle the health burden caused by viral infection. Protein synthesis from individual genes can be downregulated by synthetically deoptimizing a gene's codon usage. With more rapid and affordable nucleotide synthesis, generating viruses that contain genes with deoptimized codons is now feasible. Attenuated, vaccine-candidate viruses can thus be engineered with hitherto uncharacterized properties. With eight gene segments, influenza A viruses with variably recoded genomes can produce a spectrum of attenuation that is contingent on the gene segment targeted and the number of codon changes. This review summarizes different targets and approaches to deoptimize influenza A virus codons for novel vaccine generation.
authors.affiliation: Department of Microbiology & Immunology, University of Rochester, Rochester, NY, USA.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Baker
authors.affiliation: Department of Microbiology & Immunology, University of Rochester, Rochester, NY, USA.
authors.forename: Aitor
authors.initials: A
authors.lastname: Nogales
authors.affiliation: Department of Microbiology & Immunology, University of Rochester, Rochester, NY, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Sobrido
keywords: codon deoptimization; codon usage bias; codon-pair bias; inactivated influenza vaccines; influenza A virus; influenza reverse genetics; live attenuated influenza virus; recombinant influenza vaccine; synthetic attenuated virus engineering