Faculty Publications
Quantitative PCR Analysis of DNA Aptamer Pharmacokinetics in Mice
Document Type
Article
Journal/Book/Conference Title
Nucleic Acid Therapeutics
Volume
25
Issue
1
First Page
11
Last Page
19
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.
Department
Department of Chemistry and Biochemistry
Original Publication Date
2-1-2015
DOI of published version
10.1089/nat.2014.0515
Recommended Citation
Peters, Justin P.; Perschbacher, Katherine; Smestad, John A.; Standiford, Miranda M.; Denic, Aleksandar; Wootla, Bharath; Warrington, Arthur E.; Rodriguez, Moses; and Maher, L. James, "Quantitative PCR Analysis of DNA Aptamer Pharmacokinetics in Mice" (2015). Faculty Publications. 6230.
https://scholarworks.uni.edu/facpub/6230