Quantitative PCR analysis of DNA aptamer pharmacokinetics in mice. Nucleic Acid Ther 2015 Feb;25(1):11-9
Date
12/24/2014Pubmed ID
25536292Pubmed Central ID
PMC4296750DOI
10.1089/nat.2014.0515Scopus ID
2-s2.0-84921522841 (requires institutional sign-in at Scopus site) 27 CitationsAbstract
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.
Author List
Perschbacher K, Smestad JA, Peters JP, Standiford MM, Denic A, Wootla B, Warrington AE, Rodriguez M, Maher LJ 3rdAuthor
John Smestad PhD, BS, MD Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Outbred Strains
Aptamers, Nucleotide
Area Under Curve
Base Sequence
Female
Genetic Therapy
Mice
Multiple Sclerosis
Real-Time Polymerase Chain Reaction
Sensitivity and Specificity
Tissue Distribution
