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A novel Sleeping Beauty transposase system for development of gene therapies

Dr Orsolya Barabas, European Molecular Biology Laboratory

EMBLEM


Challenge

Gene therapy has gained major interest in research and development, especially in the field of cancer immunotherapy. Sleeping Beauty (SB) is the only non-viral integrating gene delivery vector employed in gene therapy clinical trials to date. However, delivery of the SB gene increases risks of DNA-mediated geno- and cytotoxicity and provides limited control of transgenesis, hampering safe clinical application. We present a novel SB protein which overcomes these risks and provides a safer tool for the development of gene therapies, for example CAR-T cells.


Technology

Here we present SBprotAct, a safe and effective strategy based on direct delivery of the recombinant transposase protein, which enables stable and efficient mammalian cell engineering with maximal control of the transgenesis process. By rational structure-based design EMBL scientists identified a variant named high solubility SB (hsSB), which shows enhanced solubility and stability and therefore allows for large scale recombinant production. hsSB can be efficiently delivered directly into a variety of mammalian cell lines and primary cells, and executes dose-dependent transgene integration, allowing tight control of the inserted transgene copy number. hsSB acts in a hit-and-run fashion in the time window of maximum two days, minimizing the risk of undesired transposition events and genotoxicity. SBprotAct establishes a next generation of advanced SB vectors with a greatly advanced safety profile, maximal control, easy production and use, and low cost.


Commercial Opportunity

We are seeking for a partner to further exploit the potential of SBprotAct on a collaboration or licensing basis.


Development Status

The technology was demonstrated in human cell lines (HeLa), mouse embryonic stem cells (mESC), hematopoietic stem cells and primary T-cells.


Patent Situation

Priority patent application filed in August 2017.


Further Reading

www.embl.de/research/units/scb/barabas/index.html


 

A novel Sleeping Beauty transposase system for development of gene therapies