[Gene transfer--ways of administration, advantages, possible unsuitability and hazards]. / Genoverføring--administrasjonsmåter, fordeler, mulige ulemper og farer.

BACKGROUND: Reports about successful gene therapy are now published after a period of more than ten years of trial and error. The key problem is to get DNA from genes or gene fragments into the target cells to be transcribed. MATERIAL AND METHODS: A brief review of transfer techniques is given, based upon the authors' own research and the literature in the field. RESULTS: In most cases, a vector (modified virus DNA or RNA, or plasmid DNA) is used as a vehicle. Retrovirus (RNA virus), adenovirus (DNA virus) and adeno-associated virus (DNA virus) are frequently used. Non-viral vectors such as plasmid DNA, liposome-linked DNA, protein DNA conjugates and artificial chromosomes are also relevant. Retrovirus has been used in about 60% of all gene therapy protocols. One problem is how to produce enough modified retrovirus for clinical use, hence retrovirus has mainly been used in ex vivo gene therapy, in which the number of target cells to be infected with the vector is limited and much lower than in in vivo therapy. INTERPRETATION: Increased insight into the genome has taught us that genes can partially or totally replace each other with regard to function, but they will not be expressed at the same time in the patient's life or in the same organ. In the future it may not be necessary to transfer a new gene; instead we may interfere with the regulation of another gene with a similar function.

Nucleic acid vaccination of Brucella abortus ribosomal L7/L12 gene elicits immune response.

Nucleic acid vaccines provide an exciting approach for antigen presentation to the immune system. As a test of this new methodology, the immune response to the in vivo-expressed Brucella abortus ribosomal L7/12 gene in the muscle cells of mice was examined. To accomplish this goal the eukaryotic expression systems pcDNA3 and p6 were used. Single intramuscular injection of the L7/L12 gene driven by the human cytomegalovirus (CMV) promoter (pcDNA3) or bovine MHC 1 promoter (p6) resulted in intracellular expression of the B. abortus L7/L12 immunodominant protein encoded by this gene. This application facilitated directed antigen presentation to the immune system and established specific antibody and T-cell responses compared with vector only (pcDNA3) negative controls and B. abortus S19 injected positive controls. Although pcDNA3-encoded L7/L12 gene-inoculated mice possessed significant protection, p6-L7/L12 did not engender significant protection against B. abortus S2308 infection compared to positive control mice. These data suggest a promising antigen-specific response, and L7/L12 nucleic acid vaccination may be an initial step in the development of genetically engineered candidate vaccines against brucellosis. This study for the first time focuses on DNA immunization of a gene from B. abortus.