Oligonucleotide therapeutics are an emerging drug modality, which consists of modified or unmodified short nucleic acid molecules, including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNAs (miRNAs), aptamers, and DNAzymes. Oligonucleotide therapeutics can bind to an RNA target by Watson-Crick base pairing. This binding recruits RNAseH, which induces cleavage and degradation of the target RNA. The mechanism can be used to specifically change the expression of disease-relevant proteins. Thus, oligonucleotides are an attractive drug modality that has gained increasing interest in the past years.
Oligonucleotide therapeutics are made from nucleotides containing genetic code, so these therapeutics are very specific and targeted. In some cases, oligonucleotide therapeutics may be customized at an individual level. Creative Bioarray supports the development of oligonucleotide therapeutics. We have extensive experience in oligo in vitro screening using various disease relevant models.
In Vitro Oligo Efficacy Screening
We have a team of scientists dedicated to primary cell culture, custom iPSC generation, genome editing and directed differentiation to help our customers to generate their own "disease-in-a-dish" models. Using a fully optimized high-throughput workflow, Creative Bioarray tests hundreds to thousands of oligonucleotides simultaneously in vitro. This module results in the selection of oligonucleotides that induce knockdown of the target RNA in a dose-responsive manner.
Analyzing Drug Mode of Action
Insight in pathways affected by oligo administration, allows rational selection of combination therapies. Via gene expression profiling and differential gene and pathway analysis in relevant cell lines treated with candidate oligonucleotides, Creative Bioarray provides a list of genes and pathways regulated directly or indirectly by the candidate oligonucleotides.
Bioanalytical Assays
Oligo requires robust and sensitive bioanalytical assays for their quantitation in increasingly complex biological matrices, such as liver, eye, or brain tissues. The bioanalytical assay needs to ensure that there is no interference at low concentrations. Hybridization-based assay is an effective and accurate method to quantify parental oligonucleotides in circulation, and in targeted tissues.
Oligo Safety Assessment
Oligonucleotide therapeutics can also bind to unintended mRNA sequences owing to sequence homology. For this reason, knowing potential side effects and off-target-related toxicity allows you to further prioritize candidate oligonucleotides. Via in silico assessment and experimental validation of putative off-target transcripts in preclinical model systems, Creative Bioarray maps oligo off-target effects of candidate oligonucleotides and generates a list of validated off-target genes for each candidate oligonucleotide.
Advantages & Features
- We have a proven scientific background with more than 10 years of expertise in gene expression and more advanced analysis.
- We have the expertise to prioritize candidate therapeutic RNA targets in specific cell and disease types.
- Our workflow for oligo specificity analysis includes recommendations for evaluating oligo off-target effects before moving into clinical trials.
Creative Bioarray has extensive experience in modulating RNA expression. Through four unique modules, we provide expertise to support your oligonucleotide drug development pipeline. Contact us now to discuss further with our accessible and specialized team.
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