title: DNA ministrings: highly safe and effective gene delivery vectors.
abstract: Conventional plasmid DNA vectors play a significant role in gene therapy, but they also have considerable limitations: they can elicit adverse immune responses because of bacterial sequences they contain for maintenance and amplification in prokaryotes, their bioavailability is compromised because of their large molecular size, and they may be genotoxic. We constructed an in vivo platform to produce ministring DNA-mini linear covalently closed DNA vectors-that are devoid of unwanted bacterial sequences and encode only the gene(s) of interest and necessary eukaryotic expression elements. Transfection of rapidly and slowly dividing human cells with ministring DNA coding for enhanced green fluorescent protein resulted in significantly improved transfection, bioavailability, and cytoplasmic kinetics compared with parental plasmid precursors and isogenic circular covalently closed DNA counterparts. Ministring DNA that integrated into the genome of human cells caused chromosomal disruption and apoptotic death of possibly oncogenic vector integrants; thus, they may be safer than plasmid and circular DNA vectors.
authors.affiliation: 1] School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada [2] Waterloo Institute of Nanotechnology, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: Nafiseh
authors.initials: N
authors.lastname: Nafissi
authors.affiliation: School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: Samih
authors.initials: S
authors.lastname: Alqawlaq
authors.affiliation: School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Lee
authors.affiliation: School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: Marianna
authors.initials: M
authors.lastname: Foldvari
authors.affiliation: School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Spagnuolo
authors.affiliation: 1] School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada [2] Waterloo Institute of Nanotechnology, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: Roderick A
authors.initials: RA
authors.lastname: Slavcev