Designing gene therapy has never been closer. Sleeping beauty is a genome-engineering tool which is showing promise in clinical trials of therapies for lymphoma and leukemia. Now, scientists at the European Molecular Biology Laboratory (EMBL) have increased its efficiency by 30%.
Orsolya Barabas, who led the work at EMBL said that they have managed to design new variants based on the structure. Those new variants are already 30% more effective than most efficient ones currently in use.
Sleeping beauty is currently in clinical trials for B-cell leukemias and lymphomas. It is used to insert a gene into T-cells, which are white blood cells that help to find and eliminate dangers such as disease-causing microbes. These cells are harvested from a patient, and once they become genetically modified T-cells, they are injected back into the patient, where their new gene enables them to find and destroy the cancer cells. This technique is easier to apply than any current approach and is actually cheaper.
The faster the T-cells can be modified and injected back, the better the treatment prognosis for the patients, and the lower the costs. However, up until now, attempts to increase the treatment’s efficiency were just educated guesses, based on the structure of similar molecules. Franka Voigt, a postdoc in Barabas’ lab, determined the structure of Sleeping Beauty’s active domain. Collaborating with Zoltán Ivics’ lab at the Paul Ehrlich Institute in Germany, the team managed to design changes to that structure in order to make it more efficient.
Sleeping Beauty is a transposon, and like all transposons, it has an advantage for therapies that hinge on inserting a gene, compared to other genome engineering approaches such as CRISPR/Cas9. Scientists can make CRISPR/Cas9 cut the genome at a specific point, which makes it ideal for eliminating genetic errors, but it doesn’t insert any genetic material. “Ideally, you’d want to combine the targeting of CRISPR and the efficiency of Sleeping Beauty – but that’s proving very, very difficult,” said Barabas, “so it makes sense to pursue the applications that each is best at, at least for the time being.”
The researchers will continue to design mutations in order to increase Sleeping Beauty’s efficiency even more.