Virion-associated cofactor high-mobility group DNA-binding protein-1 facilitates transposition from the herpes simplex virus/Sleeping Beauty amplicon vector platform.

The development of the integration-competent, herpes simplex virus/Sleeping Beauty (HSV/SB) amplicon vector platform has created a means to efficiently and stably deliver therapeutic transcription units (termed "transgenons") to neurons within the mammalian brain. Furthermore, an investigation into the transposition capacity of the HSV/SB vector system revealed that the amplicon genome provides an optimal substrate for the transposition of transgenons at least 12 kb in length [de Silva, S., Mastrangelo, M.

Herpes simplex virus/Sleeping Beauty vector-based embryonic gene transfer using the HSB5 mutant: loss of apparent transposition hyperactivity in vivo.

The Sleeping Beauty (SB) transposon system has been successfully used as a gene delivery tool in nonviral and viral vector platforms. Since its initial reconstruction, a series of hyperactive mutants of SB have been generated. Questions remain as to whether the enhanced in vitro activities of these SB transposase mutants translate to the in vivo setting, and whether such increased integration efficiencies will ultimately compromise the safety profile of the transposon platform by raising the risk of genomic insertional mutagenesis.

Hexamethylene bisacetamide leads to reduced helper virus-free HSV-1 amplicon expression titers via suppression of ICP0.

The herpes simplex virus (HSV)-derived amplicon vector has evolved into a promising gene transfer platform for widespread DNA delivery in gene replacement strategies and vaccine development given its ease of molecular manipulation, large transgene capacity, and transduction efficiencies of numerous cell types in vivo. The recent development of helper virus-free packaging methodologies bodes well for this vector system in its eventual implementation as a clinically viable therapeutic modality. For realization of clinical application, efforts have been made to enhance yields and quality of helper-free amplicon stocks.