title: Establishment of a chimeric, replication-deficient influenza A virus vector by modulation of splicing efficiency.
abstract: Segment 8 of the influenza A virus codes for two proteins (NS1 and NS2/NEP) via splicing. Here, we developed a viral vector expressing a cytokine or chemokine instead of the interferon antagonist NS1. To achieve both the desired genetic stability and high transgene expression levels, NS2/NEP mRNA splicing efficacy had to be fine-tuned by modification of splicing elements. Expression levels of secreted foreign proteins could be further enhanced by fusing the N-terminal 13 amino acids of NS1 with an IgK-derived secretion signal peptide. Thus, the first start codon was used for translation initiation of both NS2/NEP and the foreign protein.
authors.affiliation: Avir Green Hills Biotechnology, Vienna, Austria. m.wolschek@greenhillsbiotech.com
authors.forename: Markus
authors.initials: M
authors.lastname: Wolschek
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Samm
authors.forename: Helena
authors.initials: H
authors.lastname: Seper
authors.forename: Sanda
authors.initials: S
authors.lastname: Sturlan
authors.forename: Irina
authors.initials: I
authors.lastname: Kuznetsova
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schwager
authors.forename: Alexandra
authors.initials: A
authors.lastname: Khassidov
authors.forename: Christian
authors.initials: C
authors.lastname: Kittel
authors.forename: Thomas
authors.initials: T
authors.lastname: Muster
authors.forename: Andrej
authors.initials: A
authors.lastname: Egorov
authors.forename: Michael
authors.initials: M
authors.lastname: Bergmann
mesh_terms: D003673:Defective Viruses / Q000235:genetics* / Q000502:physiology; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics* / Q000502:physiology; D009980:Influenza A virus / Q000235:genetics* / Q000502:physiology; D012326:RNA Splicing; D014779:Virus Replication