Speed up your ASO drug development with our high-throughput ASO screening platform

Supporting the development of RNA-based therapeutics

CellCarta has extensive experience in antisense oligonucleotide (ASO) drug screening with over 10,000 ASO molecules directed against more than 300 RNA targets screened to date.

Our experience encompasses various clinical-grade ASO technologies including 2’MOE-, 2’O-Me-, LNA- and cEt-modified gapmer and steric blocking ASOs.

Our modular ASO screening platform enables prioritization of ASO drugs based on ASO efficiency, off-target profile and mode-of-action information, supporting you in decision-making when progressing into (pre-)clinical studies.

ASO screening platform

We provide expertise to support your ASO drug development projects through our modular ASO screening platform which can be customized to your needs:

1. ASO screening set up

A robust screening setup increases the chances of success of every project. Our proprietary ASO design pipeline can adjust to different chemistries and takes into consideration key parameters such as target accessibility, specificity, predicted efficiency and predicted immunogenicity. ASO synthesis occurs with increasing degrees of purification depending on the goal and stage of the project.

A suitable cell line for ASO screening is selected from a predefined panel (50+ cell lines) or the cell line of your choice, considering the expression levels of the target gene. Custom assays for target gene expression profiling are designed, relying on 15+ years of expertise in qPCR assay development, for a trustworthy ASO screening readout.

2. ASO efficacy screening

Identification of the most efficient ASOs in screening libraries is key in prioritizing the most promising candidates for (pre)clinical development. We simultaneously test up to thousands of ASOs in cell cultures and assess efficiency using a fully optimized qPCR high-throughput workflow for gene expression analysis. This module results in the selection of ASOs that induce knockdown, exon skipping or upregulation of the target RNA in a dose-responsive manner.

3. ASO off-target screening

Knowing potential side effects and off-target related toxicity allows you to further prioritize candidate ASOs and decreases the chances of preclinical drug failure. we map off-target genes of up to hundreds of candidate ASOs in parallel via both in silico prediction and RNA sequencing-based empirical validation.  This module results in a list of validated off-target genes for each candidate ASO.

4. Understanding ASO mode of action (MOA)

Insights in pathways affected by ASO-treatment help understand the mode-of-action and enable rational selection of combination therapies. We perform gene expression profiling and differential gene and pathway analysis for up to hundreds of ASOs in parallel through shallow, high-throughput RNA sequencing of relevant cell lines treated with candidate ASOs.
This module results in a list of genes and pathways regulated directly or indirectly by the candidate ASOs. Our proprietary web-based tool for data visualization helps the customer to explore and understand the data.

5. Development of non-invasive companion diagnostic tests

One of the key advantages of RNA targeting therapies is that the RNA molecule is not only the therapeutic target, but also the complementary diagnostic target. Using our expertise in qPCR assay development, we can validate a robust assay to assess the circulation of the drug target in blood or plasma samples, providing a non-invasive companion diagnostic test.

RNA molecule as companion diagnostic test

One of the key advantages of RNA targeting therapies is that the RNA molecule is not only the therapeutic target, but also the complementary diagnostic target.

Using our expertise in qPCR assay development, we can validate a robust assay to assess the circulation of the drug target in blood or plasma samples, providing a non-invasive companion diagnostic test.

Recognized expertise

Our team is internationally recognized for its expertise in the field of RNA with > 20,000 citations.
Our workflow for ASO specificity analysis complies with the recommendations by the Oligonucleotide Safety Working Group:

Assessing unintended hybridization-induced biological effects of oligonucleotides. Lindow M et al. Nature Biotechnology 2012;30:920-923.

 

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