Design considerations for improved pDNA and therapeutics production

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Non-viral, plasmid DNA (pDNA) is the focus of great interest as therapeutic as well as a starting material for gene and cell therapies. The quality and quantity of the pDNA recovered from industrial processes is however affected by context-related impact of the plasmid, the presence of cryptic sequences, multimerisation leading to instability and non-optimal coiling. In this project we will work with AstraZeneca to consider how therapeutic plasmid sequences impact on the host cell and use engineering design rules to minimise such interactions while maximising plasmid replication stability and quality.The constructs of interest are already in use at AstraZeneca (AZ) and we will use transcriptomic analysis and engineering control rules to re-design them in order to achieve improved quantity and quality of the pDNA while minimising impact on the host. Lab work will entail state-of-the-art molecular cloning, transcriptomic analysis and design of CRISPR-based and RNA-based feedback controllers.