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

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