Over the last two decades, gene therapy has been successfully translated to many rare diseases. The number of
clinical trials is rapidly expanding and some gene therapy products have now received market authorisation in
the western world. Inherited metabolic diseases (IMD) are orphan diseases frequently associated with a severe
debilitating phenotype with limited therapeutic perspective. Gene therapy is progressively becoming a diseasechanging therapeutic option for these patients. In this review, we aim to summarise the development of this
emerging field detailing the main gene therapy strategies, routes of administration, viral and non-viral vectors
and gene editing tools. We discuss the respective advantages and pitfalls of these gene therapy strategies and
review their application in IMD, providing examples of clinical trials with lentiviral or adeno-associated viral gene
therapy vectors in rare diseases. The rapid development of the field and implementation of gene therapy as a
realistic therapeutic option for various IMD in a short term also require a good knowledge and understanding of
these technologies from physicians to counsel the patients at best
