The development – detailed in a study in Nature Communications – has implications for the production of cell therapies for leukaemia and lymphoma according to lead researcher, Dr Orsolya Barabas.
She told us the new versions of the transposon “create 30% more cells carrying the intended gene insertion. In principle, this means that with our new variants it should be quicker to engineer enough of a patients’ own T-cells to re-implant.”
Transposons – also known as jumping genes – are sections of DNA sequence that can change position in the genome. Synthetic transposons – like Sleeping Beauty – can be used to deliver a desired gene into a cell.
Cheaper genetic manipulation
Using transposons to modify cell lines has a number of potential advantages over viral vector-based delivery technology, including lower production cost as Barabas explained.
“Using transposons to engineer genomes for therapeutic applications is fundamentally cheaper than the current approaches that use viral gene delivery vehicles.
“This is because using transposon tools only requires two pieces of specifically designed DNA, while for the viral delivery clinical-grade viral particles carrying the appropriate cargo have to be prepared, which is expensive.
She added that: “By some estimates, production of non-viral reagents such as transposons may cost one-tenth that of GMP-grade virus.”
Barabas also expects the European Molecular Biology Laboratory's (EMBL's) Sleeping Beauty variants to reduce cell therapy production costs by cutting culturing times, although it is too early to estimate how much developers could save.
Source: Nature Communications
Title: “Sleeping Beauty transposase structure allows rational design of hyperactive variants for genetic engineering”
Authors Franka Voigt, Lisa Wiedemann, Cecilia Zuliani, Irma Querques, Attila Sebe, Lajos Mátés, Zsuzsanna Izsvák, Zoltán Ivics, Orsolya Barabas