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 III

Research output: Contribution to journalArticle

10 Citations (Scopus)

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

Fingerprint

Nucleotide Aptamers
Pharmacokinetics
Tissue
Polymerase Chain Reaction
Neurology
Tissue Distribution
Chemical analysis
Multiple Sclerosis
Central Nervous System
Animal Disease Models
Mammals
Streptavidin
Polymerase chain reaction
DNA sequences
Intraperitoneal Injections
Oligonucleotides
Animals
Proteins
Nucleotides
Molecules

ASJC Scopus subject areas

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

Cite this

Quantitative PCR analysis of DNA aptamer pharmacokinetics in mice. / Perschbacher, Katherine; Smestad, John A.; Peters, Justin P.; Standiford, Miranda M.; Denic, Aleksandar; Wootla, Bharath; Warrington, Arthur E.; Rodriguez, Moses; Maher III, L James.

In: Nucleic Acid Therapeutics, Vol. 25, No. 1, 01.02.2015, p. 11-19.

Research output: Contribution to journalArticle

Perschbacher, K, Smestad, JA, Peters, JP, Standiford, MM, Denic, A, Wootla, B, Warrington, AE, Rodriguez, M & Maher III, LJ 2015, 'Quantitative PCR analysis of DNA aptamer pharmacokinetics in mice', Nucleic Acid Therapeutics, vol. 25, no. 1, pp. 11-19. https://doi.org/10.1089/nat.2014.0515
Perschbacher K, Smestad JA, Peters JP, Standiford MM, Denic A, Wootla B et al. Quantitative PCR analysis of DNA aptamer pharmacokinetics in mice. Nucleic Acid Therapeutics. 2015 Feb 1;25(1):11-19. https://doi.org/10.1089/nat.2014.0515
Perschbacher, Katherine ; Smestad, John A. ; Peters, Justin P. ; Standiford, Miranda M. ; Denic, Aleksandar ; Wootla, Bharath ; Warrington, Arthur E. ; Rodriguez, Moses ; Maher III, L James. / Quantitative PCR analysis of DNA aptamer pharmacokinetics in mice. In: Nucleic Acid Therapeutics. 2015 ; Vol. 25, No. 1. pp. 11-19.
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