Plasmid vaccines and therapeutics: from design to applications.
In the late 1980s, Vical and collaborators discovered that the injection into tissues of unformulated plasmid encoding various proteins resulted in the uptake of the plasmid by cells and expression of the encoded proteins. After this discovery, a period of technological improvements in plasmid delivery and expression and in pharmaceutical and manufacturing development was quickly followed by a plethora of human clinical trials testing the ability of injected plasmid to provide therapeutic benefits. In this chapter, we summarize in detail the technologies used in the most recent company-sponsored clinical trials and discuss the potential for future improvements in plasmid design, manufacturing, delivery, formulation and administration. A generic path for the clinical development of plasmid-based products is outlined and then exemplified using a case study on the development of a plasmid vaccine from concept to clinical trial.
Manthorpe
Marston
M
Vical Incorporated, San Diego, CA 92121, USA.
Hobart
Peter
P
Hermanson
Gary
G
Ferrari
Marilyn
M
Geall
Andrew
A
Goff
Blake
B
Rolland
Alain
A
D022122:Anthrax Vaccines / Q000008:administration & dosage* / Q000737:chemistry* / Q000235:genetics; D001483:Base Sequence; D002986:Clinical Trials as Topic; D004247:DNA; D004742:Enhancer Elements, Genetic; D006801:Humans; D008969:Molecular Sequence Data; D010957:Plasmids; D011401:Promoter Regions, Genetic; D013728:Terminator Regions, Genetic; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000737:chemistry* / Q000235:genetics
D022122:Anthrax Vaccines; D014614:Vaccines, Synthetic; D004247:DNA