[Gene transfer--ways of administration, advantages, possible unsuitability and hazards]

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.

A brief review of transfer techniques is given, based upon the authors' own research and the literature in the field.

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.

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.