Therapeutic Modalities
Oligonucleotide
Your Partner in Oligonucleotide
Drug Discovery
Safety and delivery are the main challenges associated with discovering and developing complex oligonucleotides therapies. Axcelead offers a comprehensive platform that excels in repeating both in vivo and in vitro evaluations in the short term and proposing optimal solutions to help our partners overcome these challenges.
Accelerate your oligonucleotide drug discovery and development process with Axcelead
We have a proven track record and unmatched capabilities
Sequence Design
The efficient optimization of antisense oligonucleotide (ASO) sequences for target mRNAs.
- Sequence selection combined with off-target analysis to reduce toxicity risk
- Ability of avoiding characteristic sequences with safety and toxicity concerns
- Selection of sequences that are less prone to aggregation and self-association by considering the secondary structures
- Optimization of modified nucleic acid units and modification patterns through excellent balance between activity and safety
PK Analysis & Distribution Evaluation
Insufficient drug efficacy can sometimes be attributed to poor delivery to cells within the target tissue. At Axcelead, we employ advanced techniques to investigate this issue. Through quantitative analysis and visualization utilizing IHC (immunohistochemistry) and ISH (in situ hybridization), we thoroughly evaluate the distribution of oligonucleotides at the cellular level. This approach allows us to gain valuable insights into drug delivery mechanisms and optimize treatment strategies for enhanced therapeutic outcomes.
Quantitative analysis
Based on our extensive experience, we select the most suitable methods, such as LC-MS/MS and Hybridization ELISA, and promptly report the results. In addition, we can analyze ligand-conjugated oligonucleotides and their metabolites.
Visualization by IHC and in ISH
We analyze distribution and activity at the cellular level using co-staining of ASO by IHC with anti-PS antibodies and target mRNA by ISH. It is also possible to stain the administered ASO using ISH.
POCs (peptide-oligonucleotide conjugates) Design
Peptide conjugation is an effective approach for delivering oligonucleotides to the site of action. The design and synthesis of appropriate POCs can address the challenges of delivery to targeted tissues and cells. Our extensive experience in peptide drug discovery allows us to develop POCs tailored to your specific requirements.
Contents
- Synthesis of membrane-permeable and receptor-targeting peptides
- Proposal of optimal linkers based on the characteristics of peptides
- Synthesis and purification of conjugates
Drug Efficacy Evaluation
- Various cellular assays using human cells
We have cellular assay systems for various targets or diseases using human cell lines and human-derived iPS cells to select or prioritize oligonucleotide candidates. - Drug efficacy evaluation using animal disease models
We evaluate the pharmacodynamics (PD) and efficacy of oligonucleotide candidates in animal disease models with similar causes and pathologies as the patients. - Generation of genetically-modified mice and rats
Genetically modified mice and rats with similar genes to human, using genome-editing technology including CRISPR/Cas9 system, can be efficiently generated to evaluate species-specific targets.
Safety Assessment
We have a variety of evaluation systems that cover a wide range of toxicities in oligonucleotide, aiding in the design and selection of less toxic and more effective oligonucleotides.
- Assessment of potential target-related safety issues (Target Safety Assessment)
- Evaluation of off-target toxicity (hybridization-dependent) through transcriptome analysis
- Assessment of off-target toxicity (hybridization-independent) using various toxicity assessment systems
