AI Article Synopsis
- Antisense oligonucleotides (ASOs) are rapidly emerging as important drugs, and their effective quantification is essential for drug development.
- A new branched DNA method was developed to improve the sensitivity of ASO quantification compared to traditional methods like hybridization immunoassays.
- This new method demonstrated significantly better sensitivity, achieving a lower limit of quantification (LLOQ) of 31.25 pg/ml in plasma, indicating its superiority in precision and accuracy while reducing interference from hemolysis.
Article Abstract
Antisense oligonucleotides (ASOs) are a fast-growing drug modality. Pharmacokinetic characterization and accurate quantification of ASOs is critical for drug development. LC-MS and hybridization immunoassays are common methods to quantify ASOs but may lack sensitivity. In this study we aimed to develop an ASO quantification method with improved sensitivity. We developed a branched DNA approach for ASO quantification and compared it with hybridization immunoassays. The branched DNA assay showed significantly improved sensitivity, with LLOQ 31.25 pg/ml in plasma, 6.4-and 16-fold higher than dual-probe hybridization electrochemiluminescence and single-probe hybridization ELISA, respectively, with adequate precision, accuracy, selectivity and specificity and acceptable matrix interference. Branched DNA for ASO quantification has significantly higher sensitivity and lower hemolysis interference.
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| http://dx.doi.org/10.4155/bio-2022-0035 | DOI Listing |
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