Integrated plasmid engineering and AAV manufacturing process a unified approach from lab to clinic

Plasmids are essential tools in basic research, diagnostics, and medical applications. Their versatility, ranging from traditional cloning and expression vectors to highly optimized clinical-grade DNA constructs, makes them suitable for both fundamental studies and advanced therapeutic strategies, including gene and cell therapies as well as RNA and DNA vaccines. Plasmids used in current biomanufacturing differ fundamentally depending on whether they are designed for RNA, adeno-associated virus (AAV) or lentiviral (LV) production. Indeed, certain specific nucleotide sequences, such as a poly (A) tail, inverted terminal repeats (ITRs) or long terminal repeats (LTR) that are present in plasmids form RNA, AAV and LV manufacturing can become challenging for their production and/or purification. By optimizing plasmid design and plasmid manufacturing, researchers and developers can enhance the safety, efficacy, and specificity of biotherapies, ultimately improving treatment outcomes.

Sartorius has established an integrated service platform that enables the design, construction, production, and purification of all types of plasmids used in advanced therapies. The commercialization of an optimized pHelper plasmid dedicated to the production of AAV with improved quality interms of empty/full ratio and infectivity has involved three selection steps made possible thanks to the e-Zyvec^® assembly technology, as well as an adaptation of the plasmid production method.