Structural instability of plasmid biopharmaceuticals: challenges and implications.
The global increase in the number of applications involving therapeutic plasmid DNA (pDNA) is creating a need for large amounts of highly stable and purified molecules. One of the main obstacles during the developmental stages of a new therapeutic DNA molecule involves tackling a wide array of structural instability events occurring in/with pDNA and therefore assuring its structural integrity. This review focuses on major instability determinants in pDNA. Their elimination could be considered an important step towards the design of safer and more efficient plasmid molecules. Particular emphasis is given to mutations triggered by the presence of repeated sequences, instability events occurring during plasmid intracellular routing, instability mediated by insertion sequences and host genome integration.
Oliveira
Pedro H
PH
Institute for Biotechnology and Bioengineering, Center for Biological and Chemical Engineering, Instituto Superior Técnico, Av. Rovisco Pais 1049-001 Lisbon, Portugal.
Prather
Kristala Jones
KJ
Prazeres
Duarte M F
DM
Monteiro
Gabriel A
GA
D000818:Animals; D004247:DNA / Q000627:therapeutic use*; D004355:Drug Stability; D042822:Genomic Instability; D006801:Humans; D009154:Mutation; D010957:Plasmids / Q000627:therapeutic use*
D004247:DNA