title: Analysis of plasmid DNA from a pharmaceutical perspective.
abstract: The advent of gene therapy and polynucleotide-based vaccines has resulted in the use of plasmid DNA as a drug substance. Although biologically (cell or animal) based assays must currently be employed to establish the identity and potency of such drugs, we argue that in the future, a combination of microchip-based mutation detection devices combined with an array of chromatographic, electrophoretic, hydrodynamic, and spectroscopic methods can be employed to rigorously establish these properties. We review a variety of such methods in this context and also consider the issue of the chemical stability of plasmids. Extensive comparison is made to protein-based pharmaceuticals with the unique importance of polynucleotide sequence emphasized in comparison to protein tertiary structure.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66047, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Middaugh
authors.forename: R K
authors.initials: RK
authors.lastname: Evans
authors.forename: D L
authors.initials: DL
authors.lastname: Montgomery
authors.forename: D R
authors.initials: DR
authors.lastname: Casimiro
mesh_terms: D002623:Chemistry Techniques, Analytical / Q000379:methods*; D002626:Chemistry, Pharmaceutical; D004252:DNA Mutational Analysis; D004355:Drug Stability; D005613:Freeze Etching; D005821:Genetic Techniques; D008027:Light; D018625:Microscopy, Atomic Force; D008854:Microscopy, Electron; D015394:Molecular Structure; D009691:Nucleic Acid Denaturation; D010316:Particle Size; D010957:Plasmids / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000648:ultrastructure; D017434:Protein Structure, Tertiary; D012542:Scattering, Radiation