Industrial scale production of plasmid DNA for vaccine and gene therapy: plasmid design, production, and purification

@article{Prather2003IndustrialSP,
  title={Industrial scale production of plasmid DNA for vaccine and gene therapy: plasmid design, production, and purification},
  author={Kristala Jones Prather and Sangeetha L. Sagar and Jason C. Murphy and Michel Chartrain},
  journal={Enzyme and Microbial Technology},
  year={2003},
  volume={33},
  pages={865-883}
}

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References

SHOWING 1-10 OF 178 REFERENCES
Cancer gene therapy using plasmid DNA: purification of DNA for human clinical trials.
TLDR
The scaleable purification method described here is a combination of highly reproducible unit operations; alkaline lysis, precipitation, and size-exclusion chromatography, and the advantages over existing DNA purification methods include improved plasmid purity and the elimination of undesirable process additives such as toxic organic extractants and animal-derived enzymes.
Depression of protein synthetic capacity due to cloned‐gene expression in E. coli
TLDR
The data indicate that a limitation develops within the translational capacity of the cell at high levels of cloned‐gene expression and suggest that strategies designed to enhance recombinant protein expression should include manipulation of translation as well as transcription.
High-yield production of pBR322-derived plasmids intended for human gene therapy by employing a temperature-controllable point mutation.
TLDR
The plasmid DNA isolated from this process contained lower levels of RNA and chromosomal DNA contaminants, simplifying downstream processing.
DNA and RNA-based vaccines: principles, progress and prospects.
Purification of a cystic fibrosis plasmid vector for gene therapy using hydrophobic interaction chromatography
TLDR
A new method is described for the purification of a cystic fibrosis plasmid vector of clinical grade, which includes an ammonium sulfate precipitation followed by hydrophobic interaction chromatography (HIC) using a Sepharose gel derivatized with 1,4‐butanediol‐diglycidylether.
Genetic immunization: a new era in vaccines and immune therapeutics
TLDR
It is hoped that DNA inoculation will ultimately lead to new vaccines that are immunologically effective and economically accessible to all nations.
High copy number plasmids compatible with commonly used cloning vectors.
TLDR
To maximize expression of two different gene products, the aim was to construct new cloning vectors that are compatible with many commonly used plasmids and that replicate at a high copy number.
Repressor titration: a novel system for selection and stable maintenance of recombinant plasmids.
TLDR
A novel system that employs plasmid-mediated repressor titration to activate a chromosomal selectable marker, removing the requirement for a plasid-borne marker gene is described.
...
...