Key result
A modified plasmid fermentation profile increased vector yields up to 2,600 mg/L, and dcm- strains improved transgene expression in human cells while reducing immunogenicity.
Population
Escherichia coli strains and human cells for plasmid production and transgene expression
Comparison
Modified plasmid fermentation copy number… vs Standard fermentation profile and dcm+ strains
Design
Preclinical
Authors
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May improve gene therapy vector production; leaves open clinical translation pending human studies.
Locking the plasmid methylation pattern early in product development is critical, and dcm- strains may be superior for gene therapy applications requiring reduced immunogenicity and improved expression.
Carnes et al. (2010) studied this question. Modified plasmid fermentation copy number induction profile and dcm- strains vs. Standard fermentation / dcm+ strains was evaluated on Plasmid yield, transgene expression, and immunogenicity. A modified plasmid fermentation profile increased vector yields up to 2,600 mg/L, and dcm- strains improved transgene expression in human cells while reducing immunogenicity.
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