‘Minicircle DNA will become a cornerstone of modern gene and cell therapy"

PlasmidFactory GmbH, based in Bielefeld, Germany, is recognised as a leading CDMO for the production of plasmid and Minicircle DNA. Over the past 25 years, the company has evolved from a small academic spin-off into a global reference for DNA manufacturing in gene and cell therapy. Following the launch of its new GMP facility and the clinical success of several Minicircle-based therapies, PlasmidFactory is entering a new phase—expanding its impact from plasmid DNA manufacturing toward next-generation, virus-free gene delivery. In an interation with BioSpectrum India Dr Ram Shankar, Chief Scientific Officer at PlasmidFactory, shares his insights into the company’s latest developments and the growing importance of Minicircle technology in cell and gene therapy. Editd excerpts;

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You recently presented data on Minicircle-based CART cells at the CAR-TCR Summit in Boston. What makes Minicircles such a breakthrough for gene and cell therapy?

Minicircles represent the logical next step in non-viral gene transfer. Traditional plasmids contain bacterial backbone sequences—origins of replication, antibiotic resistance genes, and other elements that are not only unnecessary for therapy but can also compromise safety and performance. Minicircles remove these bacterial sequences entirely, leaving only the therapeutic expression cassette in a small, supercoiled DNA molecule. This design has profound advantages: higher transfection efficiency, stronger and more stable expression, and significantly lower cytotoxicity. Because there are no bacterial genes, the risk of immune activation or gene silencing is minimised. The result is a cleaner, safer, and more efficient DNA vector—ideally suited for advanced therapies such as CART, TCR-T, or TIL approaches.

How do Minicircles address some of the limitations of viral vectors, such as lentivirus?

Viral vectors have enabled the first wave of gene therapies, but they come with several drawbacks—complex production, high cost, limited payload capacity, and concerns around insertional mutagenesis. Minicircles, in combination with transposon systems like Sleeping Beauty or PiggyBac, offer a virus-free alternative that is scalable, cost-effective, and safer. In recent preclinical and clinical studies, we have shown that CART cells engineered with Minicircle DNA and Sleeping Beauty transposase mRNA can eradicate tumors as efficiently as viral-vector CART cells, while integrating preferentially into genomic safe harbors. This reduces the risk of insertional mutagenesis by more than sixfold compared to lentiviral vectors. Moreover, the production of Minicircles is much faster and more economical—there is no need for complex viral packaging or biosafety-level infrastructure.