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Nucleic Acid Ther. 2017 Dec;27(6):345-353. doi: 10.1089/nat.2017.0683. Epub 2017 Sep 29.

Pharmacokinetic Properties of DNA Aptamers with Base Modifications.

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1 SomaLogic, Inc. , Boulder, Colorado.
2 Otsuka Pharmaceutical Co., Ltd. , Tokushima, Japan .


The addition of novel side chains at the 5-position of uracil is an effective means to increase chemical diversity of aptamers and hence the success rate for discovery of high-affinity ligands to protein targets. Such modifications also increase nuclease resistance, which is useful in a range of applications, especially for therapeutics. In this study, we assess the impact of these side chains on plasma pharmacokinetics of modified aptamers conjugated to a 40 kDa polyethylene glycol. We show that clearance from plasma depends on relative hydrophobicity: side chains with a negative cLogP (more hydrophilic) result in slower plasma clearance compared with side chains with a positive cLogP (more hydrophobic). We show that clearance increases with the number of side chains in sequences of ≥28 synthons, but this effect is dramatically diminished in shorter sequences. These results serve as a guide for the design of new therapeutic aptamers with diversity-enhancing side chains.


aptamer pharmacokinetics; modified nucleotides; plasma clearance; side chains

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