Our Solutions

May 2018

Altasciences Clinical Research
FAQs on Oligonucleotides
Our expert has the answers! Want to know more? ASK HER DIRECTLY!

Oligonucleotides (ONs) are commonly made in laboratories by solid-phase chemical synthesis and are short DNA or RNA molecules (oligomers) that have a wide range of applications in gene therapy.

What types of assays do ONs require?

Because tissue concentration is the main driver for the pharmacological effects of most gene therapy products, they require robust bioanalytical assays for their determination in increasingly complex biological matrices, such as brain tissue, spinal cord, colon, ocular, kidney, liver, and skin.

Which bioanalytical methods are available for ONs?

Several bioanalytical methods are available for the pharmacokinetic evaluation of ON-based products, including:

  • Hybridization ELISA
  • HPLC
  • Capillary gel electrophoresis-UV/fluorescence
  • PCR
  • LC/MS-MS based methods

The bioanalytical method you choose to use should have the required sensitivity to quantify in tissues with very low ON distribution, as well as the option of incorporating a high-throughput capacity to manage a large number of critical samples in a short time frame.

Which bioanalytical method is used at Altasciences?

After careful assessment of their advantages and limitations, Altasciences has selected the hybridization ELISA as the main approach for PK and PD determinations, since it has one of the highest levels of sensitivity, and has a high-throughput capacity, while keeping good precision and specificity. This method is validated in accordance with the FDA guidance and has been widely used to support preclinical and clinical PK and PD studies.

What are the challenges encountered during the course of clinical studies involving oligonucleotides?

Unlike conventional biological products, ONs may have specific tissue target/distribution profiles that have to be taken into account during the design of the clinical study. This will ensure that the proper bioanalytical method and matrix are selected for the bioanalysis of the clinical samples. Several bioanalytical methods and matrices may be used at the preclinical stage to fully characterize the PK profile of the ON drug and help guide discussion on clinical dosing and design. Furthermore, an understanding of the ratio between tissue and plasma concentrations obtained during the preclinical stage may help determine the level of sensitivity required for the bioanalytical method, if only plasma concentrations are going to be quantitated in the clinical study. Finally, during method validation, it is important to evaluate whether metabolites or anti-drug antibodies (ADAs) have the potential to interfere with the quantitation of the ON.

View Danielle’s presentation for more detailed information on ONs and the hybridization ELISA assay:

Quantitation of Oligonucleotides Using a Hybridization Method in Various Tissues and Species for Accurate Pharmacology and Toxicology Evaluations
Algorithme Pharma Clinical Research Vince and Associates Clinical Research Algorithme Pharma USA Clinical Research

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