The Sleeping Beauty transposon system: a non-viral vector for gene therapy

Abstract

Over the past decade, the Sleeping Beauty (SB) transposon system has been developed as the leading non-viral vector for gene therapy. This vector combines the advantages of viruses and naked DNA. Here we review progress over the last 2 years in vector design, methods of delivery and safety that have supported its use in the clinic. Currently, the SB vector has been validated for ex vivo gene delivery to stem cells, including T-cells for the treatment of lymphoma. Progress in delivery of SB transposons to liver for treatment of various systemic diseases, such as hemophilia and mucopolysaccharidoses types I and VII, has encountered some problems, but even here progress is being made.

Application of microRNAs in diabetes mellitus

“…Advances in science have led to the development of nonviral vectors-mediated gene therapies to overcome the shortcomings, e.g. the sleeping beauty transposon system (Aronovich et al 2011) and the ultrasound microbubblemediated gene delivery system (Lan et al 2003, Zhong et al 2013. Transposon-based miR-29b overexpression via mouse tail vein injection resulted in higher levels of transfection and long-term expression of miR-29b in the lungs of mice, without obvious pathological changes (Xiao et al 2012).…”

Mesenchymal Stem Cell-Based Tumor-Targeted Gene Therapy in Gastrointestinal Cancer

“…To date, the SB system has been the most widely applied. It is an efficient system that can integrate transposon DNA in diverse cell types, including human hematopoietic stem/ progenitor cells [52,53].…”

Cellular Therapies: Gene Editing and Next-Gen CAR T Cells

“…The effi ciency of integration can be greatly increased using nucleases or transposon/transposase systems (Jasin 1996 ). Stable expression using plasmids can be generated using Sleeping Beauty (SB) transposon and transposase systems (Aronovich et al 2011 ;Hackett et al 2010 ). Two DNA plasmids can be introduced to the cells: one plasmid with a transposon coding for a CAR-or TCRfusion sequence between the terminal inverted repeats that contain binding sites for the transposase and a second plasmid expressing a transposase to insert the transgene into TA dinucleotide repeats (de Jong et al 2014 ;Li et al 2013a ).…”