title: The sleeping beauty transposon vector system for treatment of rare genetic diseases: an unrealized hope?
abstract: Rare genetic diseases account for a considerable amount of fatalities and even their 'mild' or 'non-lethal' forms can produce drastic and undesirable discomfort to affected individuals. Various gene therapeutic approaches were tested for developing novel therapeutic concepts to treat these genetic diseases. Sleeping Beauty (SB) transposase represents one of these gene therapeutic systems which can be utilized for stable phenotypic correction. It is a transposable element which was resurrected and optimized for transposing genetic elements resulting in somatic integration of the transgene. Because of its versatile activity in many different organs, SB transposase has been explored for ex-vivo gene delivery and in vivo gene delivery including recently launched clinical trials based on engineered T-cells for tumor therapy and approaches to treat retinal degenerations. Here we will provide a state-of-the-art overview of preclinical studies for treatment of rare genetic diseases based on the SB transposase system for stable correction of the genetic defect. In this review, diseases affecting the blood system, the connective tissue, the immune system, the metabolism, and the nervous system and their treatment utilizing the SB transposase system will be discussed. Moreover, advantages and disadvantages of SB transposase-based gene therapeutic approaches will be mentioned. Although improvements of the SB transposase systems regarding genotoxicity and efficient delivery especially for applications in large mammals are desirable, the SB transposase system remains to hold great promise for curing rare genetic disease.
authors.forename: Philip
authors.initials: P
authors.lastname: Boehme
authors.forename: Johannes
authors.initials: J
authors.lastname: Doerner
authors.forename: Manish
authors.initials: M
authors.lastname: Solanki
authors.forename: Liu
authors.initials: L
authors.lastname: Jing
authors.forename: Wenli
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Institute of Virology and Microbiology, Center for Biomedical Education and Research (ZBAF), Department of Human Medicine, Faculty of Health, University Witten/ Herdecke, 58453 Witten, Germany. anja.ehrhardt@uni-wh.de.
authors.forename: Anja
authors.initials: A
authors.lastname: Ehrhardt
mesh_terms: D000818:Animals; D030342:Genetic Diseases, Inborn / Q000628:therapy*; D005822:Genetic Vectors; D006801:Humans; D035583:Rare Diseases / Q000628:therapy*; D019895:Transposases / Q000235:genetics*
chemical_list: D019895:Transposases; C494471:sleeping beauty transposase, human