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European Biopharmaceutical Review

Size Matters

Progressive research in gene and cell therapy, as well as DNA vaccination, requires safe pharmaceutical vectors. The former, in particular, is on the rise, with a huge potential for treating inherited disorders. However, the advances in this area depend on improved vector designs, which enable the safe delivery of therapeutics into target cells (1). The novel transfer vectors should be direct, tissue-specific, stable and highly expressive. They have to be minimally toxic, regarding anti-vector immune responses, and should not be integrated into the host genome (2). Without integration, the toxicity is low, but this also means that long-term expression – and thus therapeutic effect in mitotic cells – may not occur because of progressive loss of vector DNA (2).

Usually, viral and non-viral vectors based on plasmid DNA are used for the transfer of genetic information into the target cells. Plasmids encode these on the intracellular production of therapeutic virus particles (3). Clinical use of plasmid DNA for gene or cell therapy, as well as genetic vaccination, has been in an inferior position to viral methods, but has made significant progress in recent years (4,5).

Challenging Transfers

One limiting factor in transgene expression is the transfer process into the cytoplasm and nucleus, as the size of the DNA is crucial (6,7). The smaller it is, the better the nuclear entry. The differing proportions between two otherwise identical plasmids, such as monomer and dimer, show the influence of this procedure (8).

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Tatjana Buchholz is a certified Medical Technical Laboratory Assistant. She also has a Bachelor of Science in molecular biotechnology and a Master of Science in genome-based systems biology from the Bielefeld University, Germany. Tatjana’s bachelor’s thesis was occupied with signal studies of the promoter activity of the nuclear LHC translational repressor NAB1 in the microalgae chlamydomonas reinhardtii, and her master’s thesis was concerned with MC technology optimisation. Tatjana joined PlasmidFactory as Marketing Manager in 2016.

Dr Marco Schmeer studied chemistry and holds a PhD from the University of Bielefeld, Germany. After further postdoctoral training in the fields of electroporative gene and drug transfer, he joined PlasmidFactory as Product and Project Manager in 2005, when he was made responsible for client-related plasmid and MC production projects.

Dr Martin Schleef studied biology at the universities Würzburg and Bielefeld, Germany, and holds a PhD from the latter. He received postdoctoral training from the Institut Pasteur Paris, France, and joined QIAGEN GmbH in Hilden, Germany, in 1994. Martin is founder and CEO of PlasmidFactory, which has been a prosperous biotech company in Bielefeld since 2000. He is also a lecturer at Bielefeld University.

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Tatjana Buchholz
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Dr Marco Schmeer
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Dr Martin Schleef
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