Gene delivery from the E3 region of replicating human adenovirus: evaluation of the E3B region.
Successful therapies for cancer need to deal with the complexity associated with the human tumor. Studies of tumor and viral biology have progressed to a point where replicating viruses are now being engineered as potential treatments for human cancers. The complex nature of human cancers dictates that successful treatments will require combination therapies. To this end, we have focused on developing the gene delivery capacity of the replicating adenovirus, using the non-essential E3 region transcription unit as a target site for therapeutic transgene insertions. Utilizing the endogenous expression machinery of the E3 region (promoter, splicing, polyA) we show that a therapeutic transgene, TNF, is efficiently expressed from the E3B region and with exclusive late gene expression kinetics. Potential clinical applications are discussed.
Hawkins
L K
LK
Onyx Pharmaceuticals, 3031 Research Drive, Richmond, CA 94806, USA.
Hermiston
T
T
D017503:Adenovirus E3 Proteins / Q000235:genetics*; D001483:Base Sequence; D015153:Blotting, Western / Q000379:methods; D002460:Cell Line; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000379:methods*; D009369:Neoplasms / Q000628:therapy*; D014162:Transfection / Q000379:methods*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014779:Virus Replication
D017503:Adenovirus E3 Proteins; D014409:Tumor Necrosis Factor-alpha