Minimal piggyBac vectors for chromatin integration

In this grant, we describe novel transposon piggyBac vectors engineered to deliver transgenes as efficiently as currently available piggyBac systems, but with significantly less helper DNA co-delivered into the host genome. To generate these plasmids, we first identified an important and previously unreported aspect of transposon biology, that the full-length terminal domains required for successful plasmid-to-chromatin transgene delivery can be removed from the transgene delivery cassette without impairingtransposition efficiency, as long as these terminal domains are present somewhere within the plasmid. Transposons have the capacity to carry a large cargo load and therefore represent an alternative to retroviral and lentiviral delivery of genes. While transposons do not generate an immune response like retroviruses, current transposons still deposit large amounts of helper DNA into the host genome, DNA that can produce long-term problems due to its retained enhancer and promoter activity. In this grant,