Production of most biopharmaceuticals depends on the robust and efficient expression of the protein product from a cell line, but that’s not so easy to develop. Traditional transgene integration is inefficient and results in large efforts to identify the proper manufacturing clone. Scientists at ATUM have developed a novel solution to make cell lines that produce antibodies, as well as hard to express non-antibody proteins. Here’s how it works.
ATUM’s Leap-In Transposase® platform enables the efficient and robust transfer of DNA into a cell line, according to Claes Gustafsson, PhD, co-founder of ATUM. The technology is flexible, he says, allowing the gene of interest to be inserted in only a few copies per cell or in excess of 60 copies in a cell. Such high copy numbers trigger the expression of biotherapeutic molecules. In fact, one customer just received IND approval on a biotherapeutic created with a cell line developed with ATUM’s technology—and that’s just 18 months after the introduction of the Leap-In Transposase to the industry, he points out.
In developing a new cell line for bioprocessing, Leap-In comes with a few helpful features. For one, Gustafsson says, “Leap-In can take large amounts of DNA—up to 100-plus kilobases—and move it from a synthetic construct into the host genome. You also get more control over the expression of ratios of complex multi-chain molecules, such as an antibody’s light and heavy subunits.”
Plus, the Leap-In Transposons regularly integrate stably to DNA—compared to maybe as little as 5–10% of the time with traditional transfection—resulting in highly stable genomic insertions and protein expression resulting in reduced-risk manufacturing of complex products, claims Gustafsson.
The industry appears to agree with Gustafsson’s opinion of Leap-In’s value. “After just a year and a half of offering this technology, 10 of the top 20 pharmas have obtained a license,” he says. “This is a tool that rapidly is changing the cell line–development paradigm, and the true value is in de-risking the process.”
