Oligonucleotide Biology Platform: View our brochure here


Monomer/linker/conjugate synthesis
- Synthesis of bridged and bicyclic nucleic acids, novel amidites, and GalNAc ligands
- Oligonucleotide custom synthesis of siRNA, miRNA, ASO/gapmers, aptamers, CpG ODN, PMO, and DNA
- GalNAc-siRNA conjugation, for targeted delivery to hepatocytes
- Lipid conjugation, to increase cellular uptake and enhance stability of oligonucleotides
- Peptide conjugation of ASOs and siRNAs, to improve cell targeting and permeability
- Conjugation of oligos to small molecules, toxins, PEG, and antibodies
Oligo Library
- Library of GalNAc-conjugated siRNAs
- Custom oligonucleotide library synthesis services, including siRNA duplex libraries and PMO libraries
- Comprehensive library of special monomers
- High-throughput oligo synthesis and purification
Oligo Optimization
- Nucleobase and sugar-skeleton modifications
- Sequence substitution and back bone optimization
- Optimization of conjugation, for delivery and release
- Stability testing of siRNAs and conjugates
Target Validation and Sequence Design
- In silico sequence selection
- CRISPR library in vitro and in vivo screening
- sgRNA library screens (sgRNAi and sgRNAa)
- Cell-line engineering: overexpression, shRNA knockdown, CRISPR KO/KI
- Phenotypic profiling: cell proliferation, cell death, cell cycle profiling
- Genetically engineered mouse models
In vitro and in vivo efficacy/early tox screening, off-target
- Knockdown effect in cell lines and primary cells (mRNA & protein assessment)
- Functional evaluation via cell cycle analysis and downstream signaling pathways
- Assessment of cell-based delivery using GalNAc/ASGPR binding & uptake assays
- In vitro toxicity: immune response profiling and cytotoxicity assessment in primary human hepatocytes
- Off-target effects (transcriptome analysis): off-target profiling by RNAseq
- Quantification of siRNA in the RNA-induced silencing complex (RISC)
- In vivo PD studies in HDI, transgenic, and AAV mouse models; confirm cellular location of knockdown
- In vivo PD studies in NHPs, determine duration of knockdown effect
- Analysis of biomarkers to predict PD/efficacy studies of oligos
ADME and in vivo PK
- PK studies in mice: siRNA levels in plasma, kidney and liver quantified by stem-loop qRT-PCR
- Plasma protein binding assays and biodistribution studies
- Metabolic stability assessment and metabolite profiling/identification
- Mass balance and excretion analysis (including biliary excretion)
- Bioanalytical platforms for measuring oligo levels, including LC-MS/MS, LC-HRMS, qPCR, and ligand binding assays
Formulation
- Polymeric, lipid nanoparticles (LNPs) for siRNA and ASO delivery
- Advanced technology offering high homogeneity, robust reproducibility, and scalability for all types of liposomes
- LNPs exhibiting high encapsulation efficiency and narrow particle size distribution at <100 nm
Learn more on oligo.wuxiapptec.com
Scale-up and Manufacture
- State-of-the-art facilities supporting oligo process development and manufacturing at any scale, from nmol to mol
- Covering a variety of oligo types including, ASOs, siRNAs, aptamers, oligo conjugates, PMOs and PPMOs
- Oligo production services from lab scale to commercial scale, with more than 10 R&D production lines
Learn more on oligo.wuxiapptec.com
Toxicology
- Full toxicology capabilities, core battery of testing available
- Discovery toxicity studies include exploratory, genetic, and in vitro assays
- General toxicology studies (rodent, rabbit, dog, NHP, minipig) for 14-days, 28-days, and 13-weeks, 26/39-weeks
- TK bioanalytical method development and validation
- Immunology-related tox services, including tissue cross reactivity and Immunohistochemistry studies
Target Selection

Selection and validation of target and modality
Bioinformatics for in silico sequence pre-selection | • Overview of target: expression pattern, isoform, SNPs • Homology comparison cross species • Off-target consideration • Efficiency prediction |
Oligo design
Semi-automated in silico oligo sequence and modification design

Sequence Design for Candidate siRNAs
Transcripts of target gene Expression & Isoform | Genomic information SNP & genomic sequence |
Fragmentation | • SNP avoidance • GC ratio/distribution • Position at transcripts |
Off-target filter in human | • Genome-wide • Transcriptome-wide • Target microRNA |
Homology comparison | • NHP • Mouse/Rat |
Efficiency evaluation | • Sequence context • Thermodynamic features |
In vitro activity
- In vitro cell-based knock down assessments (transfection and free uptake)
- Splicing analysis
- Functional assays
- Tm (melting temperature) determination
- Quantification of siRNA in RISC complex
Cell Lines for Knockdown Assessment
> 400 cell lines available lines in WuXi Biology cell bank
- Patient derived cell lines
- Customized stable cell lines with lentivirus system
Primary Cells for Knockdown Assessment
- Primary human and animal hepatocytes
- Primary monkey, rat and mouse fibroblast cells; neuronal cells and muscle cells
- Customized additional primary cells available upon request
Transfection Method
- Commercial reagents
- Electroporation
Reporter assays | psiCHECK reporter assay and other reporter assays |
Evaluation of knockdown effect | • mRNA assessment by RT-qPCR, bDNA, ddPCR, capillary electrophoresis, Sanger sequencing and NGS • Protein assessment of by ELISA, Luminex, MSD, CBA, Western/Capillary Western, FACS, HCS, IF, HiBiT luciferase reporter assay, AlphaLISA, and ICW |
Tm (melting temperature) determination | FRET method with qPCR |
Cell-based functional assays | • GPCR & other receptor assays • Ion channels & transporters • Apoptosis/cell cycle • Angiogenesis • Downstream signaling pathway analysis • Cell structure and morphology analysis • Virus infection assays • Customized assays |


Early toxicology
Cytotoxicity assesment
- Cancer cell lines (HUH-1, HEPG-2)
- Non-cancer cell lines (HEK-293, HK-2, HFL-1, HUVEC)
- Cryopreserved primary human hepatocytes
Immunogenicity
- HEK-Blue-hTLR3, 5, 7, 8, 9, RIG-I, MAD5 cell-based reporter assays
- Cytokine induction and immune cell activation in PBMCs
Off target profiling
- In silico analysis
- NanoString, single-cell RNAseq analysis
- psiCHECK reporter assay
Cell viability and apoptosis | • CellTiter-Glo • LDH assay • Caspase-Glo 3/7 |
In vitro immunogenicity assays | • Cell-based reporter assays: TLRs, RIG-I and MAD5 reporter • Cytokine stimulation in hPBMCs or animal immune cells/whole blood |
Off-target effects | • PPHs transfected with siRNA; RNA extraction and analysis by RNAseq • Generation of volcano plots, heatmaps, CNET plots • Analysis of pathways not involving the target gene |


In vivo Efficacy and PK/PD studies
- Humanized mouse models
- Transgenic
- HDI
- AAV mouse models
- NHP models
- Pharmacology models
- Various dosing routes
- Short and long-term KD efficacy/pharmacology readouts
- Learn about our anti-tumor nucleic acid drug discovery platform by clicking HERE
- Read our blog: “Biological Evaluation of Oligonucleotide Drugs” by clicking HERE
- Download our White Paper: “Oligonucleotide Therapeutics: Drug Discovery Through Tightly Coupled Chemistry and Biology” by clicking HERE

Delivery and Analysis
- GalNAc-ASGPR delivery system
- SPR screening
- Customized assays for other delivery systems
- In vitro stability and protein-protein binding
- Delivery/RISC PK in mouse, rat, NHP

Oligonucleotide Synthesis & Conjugation
A One-stop Shop to Create Your ‘Monomer-Oligo-Conjugate’
- Focus on Discovery Scales to Support Early-stage Development | Accelerate Oligo-based Drug Discovery
- Delivering a broad spectrum of special monomers, diversified oligonucleotides, and custom-tailored solution for oligo-conjugation
- Special monomer synthesis bicyclic nucleic acid, stereo-defined amidite, GalNAc, PMO monomers
- Comprehensive panel of oligonucleotides: siRNAs, antisense oligonucleotide (ASO), CpG, aptamer , PMO
- Modified oligonucleotides: various bicyclic nucleic acids, 2’-modification , inverted abasic, 5’-VP
- Linker-attached oligonucleotides: single-strand and duplex with 3’- or 5’-linker modification, including amino, azido, alkyne, tetrazine, and maleimide, toward antibody conjugation.
- Long RNA sequences: up to 100 bp, >90% purity
- Oligo conjugation: siRNA and ASO with 3’- or 5’-conjugation, including GalNAc, [eptide, small molecule, cholesterol, lipid, PEG, and fluorescent tags


Learn more on oligo.wuxiapptec.com
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