TY - JOUR
T1 - Quantitative PCR analysis of DNA aptamer pharmacokinetics in mice
AU - Perschbacher, Katherine
AU - Smestad, John A.
AU - Peters, Justin P.
AU - Standiford, Miranda M.
AU - Denic, Aleksandar
AU - Wootla, Bharath
AU - Warrington, Arthur E.
AU - Rodriguez, Moses
AU - Maher, L. James
N1 - Publisher Copyright:
© Copyright 2015, Mary Ann Liebert, Inc. 2015.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - 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.
AB - 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.
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U2 - 10.1089/nat.2014.0515
DO - 10.1089/nat.2014.0515
M3 - Article
C2 - 25536292
AN - SCOPUS:84921522841
SN - 2159-3337
VL - 25
SP - 11
EP - 19
JO - Nucleic Acid Therapeutics
JF - Nucleic Acid Therapeutics
IS - 1
ER -