Table 1.

Milestones in SB-mediated therapeutic approaches

		References
Vector development
V.1	Establishment of the Sleeping Beauty (SB) transposon system	[17]
V.2	The integration pattern of SB was found to be fairly random and declared to be inherently safer in comparison to other integrating vectors	[37, 40]
V.3	First developments of improved vector components: hyperactive transposases and improvements to the inverted repeats	[24, 50–52, 112]
V.4	The enhancer/promoter activity of the transposon vector was found negligible in comparison to viral LTR	[25–26]
V.5	Proof of principle of targeted vector integration	[27, 85]
V.6	Large-scale, in vitro evolution strategy yielded a hyperactive transposase mutant – comparable efficacy to viral vectors	[31]
Delivery technologies
D.1	SB was proposed as a new generation non-viral therapeutic vector	[19]
D.2	Sustainable gene expression in primary cells (Cd34+, primary T, and human embryonic stem cells) by nucleofection	[31, 43, 69–74]
D.3	Complexing the transposon DNA with polyethylenimine (PEI)	[45, 47, 55, 59, 66]
D.4	Hydrodynamic injection	[19, 46, 65, 67]
D.5	Adaptation to the hydrodynamic delivery to a large animal (dog)	[103]
D.6	Coated nanocapsule (intravenous injection)	[49]
D.7	Proteo-liposome (intravenous injection)	[48]
D.8	Hybrid transposon/viral vectors (adeno, lenti, and herpes virus)	[65, 76–78]
Phenotypic correction in disease models
P.1	First demonstrations that a transposon could be used to correct patient’s cells (junctional epidermolysis bullosa)	[113]
P.2	Hemophilia A	[47, 49, 58]
P.3	Hemophilia B	[19, 31]
P.4	Pulmonary hypertension	[45]
P.5	Lung transplantation-associated complications	[47]
P.6	Glioblastoma	[59]
P.7	Inherited tyrosinemia	[65]
P.8	Mucopolysaccharidosis	[46, 67]
P.9	Crigler-Najjar syndrome type I	[48]
P.10	B-lymphoid malignancies	[70, 71]
Clinical application
C.1	First clinical trial approved; B-lymphoid malignancies	[80]