Antisense Oligonucleotide (ASO) Drug Development

CellCarta has extensive experience with various antisense oligonucleotide (ASO) technologies to modulate RNA expression, with over 10,000 ASO molecules screened to date.

We have proprietary knowledge to prioritize candidate therapeutic RNA targets in specific cell and disease types, built on our expertise in exploring the transcriptome. Our ASO analysis includes recommendations regarding the evaluation of ASO off-target effects before moving into clinical trials

Through our four unique modules, we provide expertise to support your ASO drug development pipeline.

1. in vitro ASO efficacy screening
   In the absence of reliable predictions, empirical identification of efficient ASOs against the RNA target of interest is required. Using a fully optimized high-throughput workflow, we simultaneously test hundreds to thousands of ASOs in vitro. This module results in the selection of ASOs that induce knockdown of the target RNA in a dose-responsive manner.
2. ASO specificity analysis
   Knowing potential side effects and off-target related toxicity, allows you to further prioritize candidate ASOs. We map off-target effects of candidate ASOs via in silico assessment and empirical validation of putative off-target transcripts in human and preclinical model systems. This module results in a list of validated off-target genes for each candidate ASO.
3. Understanding the mode of action (MOA)
   Insight in pathways affected by ASO administration allows rational selection of combination therapies. Via gene expression profiling and differential gene and pathway analysis in relevant cell lines treated with candidate ASOs, we provide a list of genes and pathways regulated directly or indirectly by the candidate ASOs. This module provides direct insights in pathways in which the therapeutic target plays a role.
4. 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 companion or complementary diagnostic target. Via gene expression profiling of blood or plasma samples, we assess the circulation of the (cleaved) target, providing a non-invasive test.

Our team is internationally recognized for its expertise in the field of RNA and our workflow for ASO specificity analysis was recommended by the Oligonucleotide Safety Working Group in a publication:

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

Digital PCR

Quantitative PCR