In the Zone: oligonucleotide therapy quantitation
The development of oligonucleotide therapies for the treatment of genetic diseases through modulation of gene expression is rapidly expanding, with 22 approved therapies currently and a growing pipeline representing hundreds of new molecules in development. The expansion of these development programs has presented bioanalytical scientists with challenges when measuring therapeutics in preclinical and clinical samples, with analysis requiring high sensitivity and matrix tolerance towards serum, tissue homogenates, cerebral spinal fluid and plasma.
LC–MS has traditionally been used but drawbacks with insufficient sensitivity and extensive sample extraction limit its utility. High-sensitivity qPCR has also been utilized due to its low detection limits, but accuracy and precision have been problematic, along with the inability to distinguish metabolites from the parent molecule. Ligand-binding assays using hybridization approaches are attractive alternatives since they are 100–1000 times more sensitive than LC–MS. However, ELISAs offer a limited assay dynamic range and include time-consuming manual pipetting and incubation steps. The Gyrolab microfluidic immunoassays solve problems of manual assay pipetting and incubation steps and provide the low picogram sensitivity and 3–4 log dynamic ranges required.
The Gyrolab Mixing CD fully automates the hybridization-based oligonucleotide therapy quantitation assay in biologic matrices, where a streptavidin-coated bead captures the biotin-labeled antisense oligo and uses a complementary oligo detection probe labeled with Alexa-fluor 647 for automated, laser-induced fluorescence detection. The flow-through column design brings high matrix tolerance and automation meets the need for efficient and reproducible walkaway bioanalysis assays to keep up with the increased demand for improved approaches to oligonucleotide therapeutic bioanalysis.
[Video by Peter Halliday]
INFOGRAPHIC
Infographic: Gyrolab® hybridization assays for oligonucleotide analysis
In this infographic, we explore how Gyrolab’s fully automated hybridization-based oligonucleotide therapy quantitation assay helps to meet the increasing demand for improved approaches to oligonucleotide therapeutic bioanalysis, expanding the landscape of genetic disease therapeutics.
INTERVIEW
Using the Gyrolab® platform for oligo quantification: an interview with John Chappell
In this interview, we spoke to John Chappell, Senior Global Scientific Support Manager at Gyros Protein Technologies (Uppsala, Sweden) about his experience working with the Gyrolab platform for oligonucleotide assays.
RESOURCES
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