PlasmidFactory and MDCell partnership to continue

Harnessing jumping genes to advance gene-therapy cancer treatment: In an effort to optimize the Sleeping Beauty system, the MDCell – Helmholtz Innovation Lab and PlasmidFactory are extending their collaboration.

If you want to modify a human body’s immune cells – for example by giving them new vitality to fight a tumor or stop an autoimmune disease – you need safe and reliable tools. One such tool is the Sleeping Beauty system developed at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC). The MDCell – Helmholtz Innovation Lab and the biopharmaceutical company PlasmidFactory are working together to improve this system.

“Sleeping Beauty 100x” is based on an element in the genome of fish that is probably 20 million years old. Known as a “jumping gene,” or transposon, it was able to copy itself and change positions within fish DNA. Transposons alter genetic identity and are thus considered one of the motors of evolution. Dr. Zsuzsanna Izsvák and her colleagues have woken this jumping gene from its deep evolutionary sleep, increased its activity a hundredfold and developed it for gene therapy. The “Sleeping Beauty” system can now introduce genes into the genome. According to Izsvák, it is safer, cheaper and more efficient than other methods.

The modified gene sequence does not need a virus, acting like a “taxi” (vector), to carry it to its destination. Instead, the system is composed of two elements: the pT4 transposon – a circular DNA molecule (plasmid) into which the desired gene is inserted between two typical markers – and the genome of an enzyme named “SB100x,” which cuts the desired gene out of the plasmid and escorts it to the new site.

MDCell and PlasmidFactory are improving this system to make it safer for use in humans. One innovation is to copy the genome of the SB100x enzyme while it is still in the petri dish and to add it – in the form of in-vitro transcribed RNA (IVT RNA) – to the cells that are be modified. The pT4 transposon is also no longer a complete plasmid, as is often the case in bacteria. This led PlasmidFactory to develop a technique for creating a minicircle that, except for the necessary markers, is composed almost entirely of the gene that is to be inserted.

“The fact that the bacterial elements of the plasmids are missing is very important. It makes the SB100x transposon system even safer and more effective,” says Dr. Holger Hoff, the director of MDCell. “And PlasmidFactory produces minicircles of very high quality; this is because they are tightly woven together.”

Both parties bring extensive experience to the partnership. PlasmidFactory is the expert in designing and copying these “gene taxis”. “In our special laboratory in Bielefeld, we’re currently establishing methods to produce high-quality minicircle DNA for use in CAR T-cell therapy research,” explains Dr. Martin Schleef, CEO of PlasmidFactory. The goals of the partnership include using Sleeping Beauty to genetically modify immune cells so they will help sick people recover, and making the system ready for use in hospitals.

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