Quantitative PCR analysis of DNA aptamer pharmacokinetics in mice

Katherine Perschbacher, John A. Smestad, Justin P. Peters, Miranda M. Standiford, Aleksandar Denic, Bharath Wootla, Arthur E. Warrington, Moses Rodriguez, L. James Maher

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)11-19
Number of pages9
JournalNucleic Acid Therapeutics
Volume25
Issue number1
DOIs
StatePublished - Feb 1 2015

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Drug Discovery

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  • Cite this

    Perschbacher, K., Smestad, J. A., Peters, J. P., Standiford, M. M., Denic, A., Wootla, B., Warrington, A. E., Rodriguez, M., & Maher, L. J. (2015). Quantitative PCR analysis of DNA aptamer pharmacokinetics in mice. Nucleic Acid Therapeutics, 25(1), 11-19. https://doi.org/10.1089/nat.2014.0515