Sleeping Beauty–baculovirus hybrid vectors for long‐term gene expression in the eye

Abstract

Our results confirm that (i) SB-baculovirus hybrid vectors mediate long-term gene expression in vitro and in vivo, and (ii) the hybrid vectors are potential new tools for the treatment of ocular diseases.

Going non-viral: theSleeping Beautytransposon system breaks on through to the clinical side

“…Finally, similar to adenovirus, baculoviral vectors can efficiently transduce many cell types, but can only provide transient expression in the absence of stable genomic integration. Hybrid baculovirus/SB vectors have been shown to confer prolonged transgene expression in human cells both in vitro and in vivo in intratumoral injections in xenograft mice (Luo et al, 2012), as well as in vivo in the mouse eye (Turunen et al, 2014). Note that, although these hybrid virus/SB transposon vectors may provide advantage from a technical point of view (non-toxic delivery of the SB vector components into target cells), their application would lose all the advantages of a fully non-viral system that we outlined above.…”

Gene Therapy with the Sleeping Beauty Transposon System

“…In principle, these hybrid vectors could be used as alternatives to established viral vectors, and are suitable for cell type-specific gene engineering. Viral transposon hybrids have been established for integrase deficient lentivirus (IDLV) [70][71][72], adenovirus [73,74], AAV [75], herpes simplex virus [76,77], and baculovirus [78,79], where the SB transposon provides stable gene integration. Especially for in vivo approaches, hybrid vectors could be advantageous, because they: (i) bypass the need for repeated vector administration due to stable chromosomal transgene integration and expression; and (ii) may allow reduction of the applied viral dose, thereby alleviating vectorassociated immune complications.…”

Sleeping Beautytransposition: from biology to applications

“…For instance, the mutagenic potential of MLVbased vectors have been reported in multiple clinical gene therapy trials: SCID-X1 (Hacein-Bey-Abina et al, 2003), (Deichmann et al, 2007;Hacein-Bey-Abina et al, 2008;Howe et al, 2008;Thrasher et al, 2006), X-CGD (Stein et al, 2010) and WAS (Braun et al, 2014). Furthermore, recent analyses also demonstrate that HIV (Yant et al, 2002) AAV/SB Recombinant AAV (Zhang et al, 2013) HSV-1 amplicon/SB HSV-1 (Bowers et al, 2006;de Silva et al, 2010a;de Silva et al, 2010b;Peterson et al, 2007) Baculo/SB Baculovirus (Luo et al, 2012;Turunen et al, 2014) IDLV/SB IDLV (Moldt et al, 2011;Staunstrup et al, 2009;Vink et al, 2009;) Adeno: adenovirus; AAV: adeno associated virus; IDLV: integrase defective lentivirus; HSV-1: herpes simplex virus 1 amplicon; baculo: baculovirus Note: The transposase (highlighted in green) and the transposon (highlighted in red) plasmids can be packaged into various recombinant viruses. A colored version is available online (www.informahealthcare.com/bmg).…”

“…To circumvent these problems, a hybrid baculovirus/SB vector was generated for efficient mammalian cell transduction and sustained transgene expression (Luo et al, 2012;Turunen et al, 2014) (Figure 8 and Table 1). The baculovirus-SB vector combines the efficient baculovirus transduction with SB-mediated gene expression, alleviating the shortcoming of conventional baculovirus vectors.…”