title: Quantitative PCR analysis of DNA aptamer pharmacokinetics in mice.
abstract: DNA aptamer oligonucleotides and their protein conjugates show promise as therapeutics in animal models of diseases such as multiple sclerosis. These molecules are large and highly charged, raising questions about their biodistribution and pharmacokinetics in mammals. Here we exploit the power of quantitative polymerase chain reaction to accurately quantitate the tissue distribution of 40-nucleotide DNA aptamers and their streptavidin conjugates after intraperitoneal injection in mice. We show remarkably rapid distribution to peripheral tissues including the central nervous system. Modeling of tissue distribution data reveals the importance of DNA aptamer sequence, 3' modification, and protein conjugation in enhancing tissue exposure. These data help to interpret the previously observed effectiveness of aptamer conjugates, as opposed to free aptamers, in stimulating central nervous system remyelination in a mouse model of multiple sclerosis.
authors.affiliation: 1 Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine , Rochester, Minnesota.
authors.forename: Katherine
authors.initials: K
authors.lastname: Perschbacher
authors.forename: John A
authors.initials: JA
authors.lastname: Smestad
authors.forename: Justin P
authors.initials: JP
authors.lastname: Peters
authors.forename: Miranda M
authors.initials: MM
authors.lastname: Standiford
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Denic
authors.forename: Bharath
authors.initials: B
authors.lastname: Wootla
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Warrington
authors.forename: Moses
authors.initials: M
authors.lastname: Rodriguez
authors.forename: L James
authors.initials: LJ
authors.lastname: Maher
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D052157:Aptamers, Nucleotide / Q000235:genetics / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001483:Base Sequence; D005260:Female; D015316:Genetic Therapy; D051379:Mice; D009103:Multiple Sclerosis / Q000628:therapy; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D052157:Aptamers, Nucleotide