Gene Therapy of Single-gene Disorders: Preface to the

Abstract

Gene therapy was introduced into clinical practice with great excitement, much publicity and considerable optimism in the early 1990s. Scientific evaluation of the early clinical trials has, however, greatly reduced the initial optimism. Follow-up studies have revealed that many early gene therapy trials mainly represented gene transfer into patients, possibly with short-term effects, but not true gene therapy where the course of the disease is permanently affected. This has lead to critical re-evaluation of the approaches taken. Clearly, more basic understanding is needed of the molecular mechanisms of the diseases treated. For this purpose, better animal models for human diseases are necessary. One of the biggest obstacles for gene therapy has been the lack of adequate vector systems. Development of new vectors for efficient and targeted delivery and uptake of therapeutic genes is a crucial area where progress needs to be made. The rationale for gene therapy depends largely on the type of disease to be treated. Recessively inherited single-gene disorders represent diseases where the concept of gene therapy-addition of a therapeutic gene to restore the lost function of two mutant alleles-is easily understood and rarely questioned. However, most gene therapy protocols are focused on multifactorial diseases such as malignancies where the therapeutic approach is quite different. While gene transfer technologies are being developed into truly effective gene therapy, the fight against inherited single-gene disorders also continues at population level by carrier screening and prenatal diagnostics where rapid methodological developments are taking place.

Key Words:

• gene therapy
• inherited diseases
• knock-out animals
• prenatal diagnostics
• transgenic animals