Oligonucleotide Analysis

Oligonucleotide Analysis Tools

Artistic rendering of an oligonucleotide

Overview

Literature

Application Notes

A Diverse Growing Landscape

From Antisense, siRNA, gRNA, and more to GMP oligonucleotide primers and probes
As the pipeline for oligonucleotide-based therapeutics continues to expand, as does demand for GMP oligos for clinical diagnostics, there is a growing need for analytical tools and workflow solutions that deliver high quality results, improve efficiency, and enable regulatory compliance.

Meeting Analytical & Regulatory Requirements

Compliance-ready solutions covering data acquisition, processing, and reporting
For oligonucleotides being developed as therapeutics, or for clinical diagnostics, there are regulatory requirements to confirm product ID, sequence, and purity. With therapeutic modalities comes the added requirement of identifying, characterizing, and quantifying low-level impurities as well as pre-clinical and clinical DMPK studies (BioA, MetID) to ensure drug safety and efficacy.

Optimized LC-MS workflows for oligonucleotide analysis from characterization to QC

Chemically Modified Nucleotides

Delivering enhanced drug stability and efficacy
The incorporation of chemically modified nucleotides is shown to dramatically improve the stability and efficacy of oligonucleotide-based drugs and has been key to their success and regulatory approval in recent years. Confirming the identity and location of these modifications in the oligonucleotide sequence is therefore of critical importance, and mass spectrometry has the unique ability to provide 100% sequence confirmation, including the location of each modified nucleotide within the sequence.

Conjugated Species For Targeted Delivery

Delivering the API into the targeted cells
Oligonucleotide-based drugs (with the exception of aptamers) must be delivered into targeted cells within the body in order to work. To achieve this, they are increasingly conjugated to other molecules (e.g.: GalNac, cholesterol, antibodies, peptides, et.al.) that bind to receptors found on targeted cells. Once bound to a targeted cell receptor, the conjugated form is engulfed by the cell and the oligotherapeutic is subsequently released within the cell. LC-MS workflows play a critically important role in the development and characterization of these conjugated forms.

Sample Prep

Tools for enhanced recovery, repeatability, and productivity
For quantitative analyses in particular, good sample preparation is key to achieving maximum recovery, consistency, and lower limits of detection. Waters offers a range of sample preparation tools that enhance recovery and repeatability and that enable greater productivity.

Featured Technology: Andrew Alliance Automated Liquid Handling, Otto SPEcialist, Oasis µElution SPE Plates, QuanRecovery Collection Vials/Plates

Separations

ACQUITY Premier Solution for unparalleled oligonucleotide separations performance
As negatively charged molecules, oligonucleotides are prone to metal interactions that can negatively impact LC separations and detection performance. Conditioning and passivation procedures routinely run to mitigate these interactions reduce equipment utilization and put a drag on productivity. Our ACQUITY Premier Columns and Systems greatly reduce the impact of non-specific adsorption (NSA) on oligonucleotide separations, improving sensitivity and repeatability.

Featured Technology: ACQUITY PREMIER Columns and System, BioAccord LC-MS System, MassPREP Standard

Product image of the ACQUITY Premier Solution

Mass Analysis

Fit-for-purpose LC-MS workflows
From characterization to production monitoring, DMPK studies, QC release and more, Waters offers a range of LC-MS workflows that deliver maximum robustness, sensitivity, and repeatability. Automated compliance-ready data acquisition and processing tools streamline data analysis and reporting, and facilitate the sharing of data/information across systems, labs, and geographies for enhanced productivity and reduced risk.

Featured Technology: BioAccord LC-MS System, XEVO G2-XS QTof, Xevo TQ XS Tandem Quadrupole, SYNAPT XS MS Platform

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Select Science Webinar

Intact Mass Analysis of Modified Oligonucleotides and Impurities
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Bioanalytical Method Development for Oligonucleotides
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Waters Webinar

Considerations for Developing IP-RP Methods for Oligonucleotide Analysis
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Application Solutions

Oligonucleotide Applications Notebook
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