+1 (888) 794-0077

Oligonucleotide Solutions

Oligonucleotides are short single or double-stranded fragments of DNA or RNA molecules that have a wide range of potential applications—including neurology, oncology, viral infections, and rare genetic disorders. Our comprehensive testing services cover the entire spectrum of oligonucleotides, from discovery through IND and NDA, allowing you to advance novel therapies further, faster.

Oligonucleotide Solutions Tested by WuXi AppTec Lab Testing Division

Oligonucleotide IND Packages

Oligonucleotide In Vitro Studies

In Vivo Studies

Comprehensive Preclinical
Testing for Oligonucleotides

Due to their unique chemical structure and mechanism of action, oligonucleotides require specialized preclinical testing methodologies and custom studies based on specific characteristics of each oligonucleotide. WuXi AppTec can support every aspect of your oligonucleotide development from IND to NDA – all conveniently available under one roof.


Access a global network of testing facilities for oligonucleotide DMPK research, focusing on tailored solutions for structure modification and delivery systems.


Put your oligonucleotide candidate on the right track with a bioanalytical strategy designed to establish and execute the right methods for regulatory submission.


Our integrated safety assessment services provide multidisciplinary expertise and experience that saves time and cost while yielding the valuable data you need.


We support your CMC authoring needs, in both the US and China, from preclinical to commercial lifecycle management for both drug substance and product.


Get validated discovery assays, including in vitro assays and in vivo disease models in cardiovascular, CNS, respiratory, metabolic, and infectious diseases.

Regulatory Affairs

Make global filings convenient, efficient, and cost-effective across US FDA, NMPA, and EMA with our extensive regulatory submission support.

End-to-End Preclinical Services

WuXi AppTec offers a comprehensive testing platform for oligonucleotides, including bioanalysis, biomarker analysis, in vitro and in vivo metabolite identification, and radiolabeled non-clinical ADME and clinical AME study capabilities. Testing platforms include mass spectrometry, qPCR, and fluorescent probes, and biomarkers include target mRNA, target proteins, or downstream biomarkers.

Custom Study Strategies

Our team specializes in designing customized study strategies for oligonucleotide molecules, integrating insights from DMPK, bioanalysis, and safety assessment. We offer rapid optimization and timely adjustments, leveraging flexible study concepts to meet evolving project needs. Our approach ensures comprehensive support throughout the preclinical development process, enabling efficient advancement of oligonucleotide therapeutics.

Global Partner & Network

WuXi AppTec is a true global provider in preclinical large molecule solutions, with state-of-the-art facilities and experts across US, Europe, and China. We have decades of experience operating within diverse regulatory environments and delivering tailored testing solutions that advance large molecules from preclinical through IND, NDA and beyond.

Frequently Asked Questions

What are oligonucleotides?

Oligonucleotides are short single or double-stranded fragments of DNA or RNA molecules. Oligonucleotide-based therapies are rapidly emerging as a promising frontier in drug development, offering versatile solutions for a wide spectrum of diseases.

What are the biggest therapeutic opportunities related to oligonucleotides?

Oligonucleotide-based therapies are rapidly emerging as a promising frontier in drug development, offering versatile solutions for a wide spectrum of diseases. Key opportunities include:

  • Antisense Oligonucleotides (ASOs): Targeting neurology, oncology, and rare genetic disorders, ASOs hold the potential for modulating gene expression and addressing diseases at the RNA level.
  • RNA Interference (RNAi) Therapies: With applications in viral infections and metabolic disorders, RNAi therapies leverage the natural cellular mechanism to silence specific genes, offering precise and targeted treatment approaches.
  • Messenger RNA (mRNA) Therapies: From developing vaccines, such as the highly successful COVID-19 vaccine, to advancing cancer immunotherapies, mRNA therapies harness the body’s own machinery to produce therapeutic proteins, offering rapid and adaptable solutions for disease prevention and treatment.

Why is preclinical testing important for oligonucleotides?

Preclinical testing is essential for oligonucleotides to assess their stability, target specificity, and potential off-target effects. It ensures that these molecules can effectively modulate gene expression without causing unintended toxicities, providing critical data on their pharmacokinetics and pharmacodynamics. This testing is crucial to confirm their therapeutic potential and safety profile before advancing to human trials.

Why is preclinical testing important for oligonucleotides?

In preclinical development, the diverse types of oligonucleotides exhibit varying pharmacokinetic properties influenced by mechanisms, delivery systems, and chemical modifications. Tailored study strategies are essential to expedite development, focusing on the specific characteristics of each oligonucleotide.

Compared to “standard” small molecule or biologics, preclinical testing for oligonucleotides involves specialized methodologies and considerations due to their unique chemical structure and mechanism of action. This includes the need for customized analytical methods, evaluation of sequence-specific effects, and careful assessment of safety and off-target effects.

What are some challenges of oligonucleotide development and testing?

  • Diverse types: The different chemical modifications, sequences, or delivery systems of oligonucleotides may have their respective specificities, thus requiring different pharmacokinetic evaluation methods.
  • Complex sample pretreatment: It is difficult to establish a proper mass spectrometry analysis method due to its poor stability, matrix effect, ion inhibition, and metabolite interference.
  • Analytical method development: Oligonucleotides require specialized analytical methods for characterization and quantification due to their unique properties, such as sequence specificity and potential for chemical modifications. Tailored methods will be needed for some specific oligonucleotide sequence and intended application.
  • Off-Target Effects: Oligonucleotides have the potential to bind to unintended targets, leading to off-target effects that may result in adverse reactions or toxicity. Identifying and characterizing off-target binding sites and assessing their potential impact on safety can be challenging, requiring advanced analytical techniques and comprehensive screening approaches.
  • Immunogenicity: Oligonucleotides can stimulate the immune system, triggering immune responses such as antibody formation or cytokine release. Assessing the immunogenicity of oligonucleotide therapeutics and predicting potential immune-related adverse events pose challenges in preclinical studies.
  • Non-final regulatory guidelines: Neither FDA nor ICH has formulated final specific guidelines for the preclinical study of oligonucleotides.

What types of preclinical studies are essential for oligonucleotides?

Essential preclinical studies for oligonucleotides include toxicity assessments, pharmacokinetics (PK) and pharmacodynamics (PD) studies, biodistribution analyses, efficacy studies in relevant animal models, and immunogenicity evaluations. These studies ensure oligonucleotide stability, target specificity, and safety before clinical trials.

What safety assessments are critical in the preclinical testing of oligonucleotides?

Critical safety assessments in the preclinical testing of oligonucleotides include acute and chronic toxicity studies, genotoxicity tests, immunotoxicity evaluations, and organ-specific toxicity assessments. These tests help identify potential adverse effects and ensure the oligonucleotide’s safety profile before human trials.

What considerations are important for DMPK studies on oligonucleotides?

For DMPK studies, selection of an appropriate in vitro metabolic model is crucial, guided by the drug’s structural features. In vivo PK investigations involve exploring different administration methods to assess pharmacokinetic properties effectively. Moreover, developing suitable detection methods aligned with oligonucleotide properties is paramount across DMPK, bioanalysis, and toxicology assessments.

How do you analyze an oligonucleotide’s off-target effects?

Off-target effects of oligonucleotides are analyzed through various methods such as computational prediction algorithms, in vitro binding assays, transcriptomic analyses, and in vivo studies using animal models. These approaches help identify unintended interactions with non-target nucleic acids, proteins, or cellular pathways, ensuring the oligonucleotide’s specificity and safety.

What regulatory guidelines must be followed for preclinical testing of oligonucleotides?

Neither FDA nor ICH has formulated final specific guidelines for the preclinical study of oligonucleotides. However, testing must follow GLP regulations and ICH guidelines to ensure the quality, integrity, and reliability of preclinical data. Draft guidances, such as the FDA’s “Clinical Pharmacology Considerations for the Development of Oligonucleotide Therapeutics,” should be consulted during the development of the oligonucleotide test plan.

What are the potential pharmacological concerns of oligonucleotides?

Potential pharmacology concerns with oligonucleotides include off-target effects leading to unintended gene silencing or modulation, immunogenicity triggering immune responses, non-specific interactions with cellular components, challenges related to delivery and distribution to target tissues, and the risk of QTc interval prolongation, which can result in serious cardiac arrhythmias. Addressing these concerns is crucial for optimizing the therapeutic efficacy and safety of oligonucleotide drugs.

How is the pharmacokinetics of oligonucleotides evaluated in preclinical testing?

The pharmacokinetics of oligonucleotides in preclinical testing is evaluated through various methods, including measuring their plasma concentration-time profiles after administration, assessing tissue distribution, evaluating metabolic stability, determining clearance rates, and studying excretion pathways. These analyses provide insights into the ADME properties of oligonucleotides, informing dosing regimens and preparing for human trials.

What efficacy tests are conducted for oligonucleotides in preclinical studies?

Efficacy tests conducted for oligonucleotides in preclinical studies include assessing their ability to modulate target gene expression or protein levels, evaluating therapeutic effects in disease-relevant animal models, and measuring relevant biomarkers or physiological endpoints associated with the desired therapeutic outcome. These studies aim to demonstrate the efficacy of oligonucleotide therapeutics in preclinical settings, providing rationale for further clinical development.

What analytical methods are used in oligonucleotide preclinical testing?

Analytical methods used in oligonucleotide preclinical testing include techniques such as polymerase chain reaction (PCR) for target gene expression analysis, high-performance liquid chromatography (HPLC) or mass spectrometry (MS) for quantifying oligonucleotide concentrations in biological samples, gel electrophoresis for assessing purity and integrity, and bioanalytical assays for measuring pharmacokinetic parameters. These methods ensure accurate characterization of oligonucleotide properties and responses in preclinical studies.

Let’s Talk About Your Oligonucleotide Program

Have questions? Need specific assays? Talk to an expert today about your oligonucleotide needs.