Lessons Learned from Gene Therapy Concerning and the Use of Integrating Vectors and the Possible Risk of Insertional Oncogenesis

摘要

A number of clinical trials are being performed using vectored vaccines and nucleic acid vaccines intended to protect against infectious diseases. Nucleic acid vaccines used in vivo are typically bacterial plasmid DNAs prepared form E. coli cells encompassing an expression vector which harbours a CMV promoter driving the expression of a viral, parasitic or bacterial antigen gene and a bovine growth hormone gene-derived poly-adenylation site. Newer nucleic acid vaccines no longer contain antibiotic resistance genes because such genes are not recommended to be used in humans. Preventive vectored vaccines are viral vectors used in vivo, many of them inoculated s.c. or i.d. They mainly include replication-incompetent adeno-associated viral (AAV) vectors, adenoviral vectors and poxviral vectors encompassing an expression vector encoding one or several antigens derived from a human pathogen. The expression vector mediates the expression of antigens in the transduced cells, thus mediating the induction ofan immune response.