Custom Oligonucleotide Synthesis

Research and Development of ASOs, siRNA, and PMOs

OLIGO Services

Custom Oligo Synthesis Services

Sinopep's oligonucleotide CRDMO platform, situated in Hangzhou Biopharma Town, which boasts a highly qualified research team, with more than half of its members holding master's degrees or higher. The platform has achieved significant milestones in oligonucleotide development, including the successful synthesis of various types of oligos such as ASO, SiRNA, and PMO. Additionally, the platform has collaborated with international companies to produce the first generic drug of oligonucleotides, marking a groundbreaking achievement.

We offer research-grade and clinical-grade oligonucleotide manufacturing services, supporting clients from early discovery through clinical development. Utilizing solid- and liquid-phase approaches, we provide custom oligo contract development and manufacturing, including scale-up production and comprehensive analytical testing.

Oligonucleotide Types

Full-spectrum custom synthesis capabilities supporting diverse therapeutic modalities, delivering high-purity ASOs, modified siRNAs, and conjugated architectures optimized for therapeutic development.

Oligo Type Supported Variants Mechanism & Significance
Antisense (ASO) Gapmers, Mixmers RNase H-mediated mRNA cleavage & pre-mRNA splicing modulation.
siRNA Duplex siRNA, asymmetric siRNA RISC-mediated catalytic mRNA degradation for post-transcriptional silencing.
miRNA Agomirs, Antagomirs Endogenous microRNA regulation via direct mimicry or steric inhibition.
Morpholinos (PMO) PMO, PPMO (Peptide-conjugated) Uncharged backbone preventing enzymatic cleavage for exon skipping.
Aptamers DNA Aptamers, RNA Aptamers High-affinity molecular targeting against specific proteins and cell receptors.
CpG Oligos Class A, Class B, Class C CpG ODNs TLR9 receptor activation to stimulate innate and adaptive immune responses.
Decoy Oligos Double-stranded DNA decoys Competitive binding to transcription factors to inhibit pathogenic gene expression.
Peptide-Oligo Conjugates POCs, Cell-Penetrating Peptides Enhanced biological membrane transit and targeted tissue internalization.
tRNA & gRNA sgRNA, crRNA, tracrRNA CRISPR-Cas genome editing complexes and translational Machinery support.
Circular & Branched Oligos circRNA mimics, Dendromers Exonuclease degradation resistance and high-density functional group display.

Oligonucleotide Modificatons

Precision chemical modification platforms engineered to optimize metabolic stability, enhance cellular targeting, and maximize therapeutic efficacy across custom oligonucleotide sequences.

Modification Category Available Options Key Technical Benefit
Base & Sugar Modifications 2′-OMe, 2′-MOE, 2′-F, 2′-LNA, cEt, 5mC, dU, dI, Pseudouridine (Ψ), N1-methyl-Ψ Duplex stability, nuclease resistance, cross-linking, immune evasion
Backbone Linkages Phosphorothioate (PS) bonds, Phosphorodithioate (PS2), Mesyl phosphoramidate Exonuclease & endonuclease protection
Phosphorylation & Cap Modifications 5′ Phosphorylation, 3′ Phosphorylation, 5′-Vinylphosphonate (5′-VP), Inverted dT (3′-3′) Ligase substrate (5′), extension blocking (3′), RNAi activity, terminal cap degradation resistance
Targeting & Lipid Conjugates GalNAc (tri-antennary), Cholesterol, Fatty Acids (C16, C18, C22), Tocopherol, Folate Hepatic tissue delivery, cellular uptake, endosomal escape, extended circulation
Linkers Amino modifiers (C3, C6, C12), Biotin, Biotin TEG, Thiol groups (S-S), Carboxyl, Maleimide Covalent attachment & conjugation
Spacers C3, Spacer 6, Spacer 9, Spacer 12, Spacer 18, dSpacer (Abasic), PC Spacer Spatial distance control, abasic site mimicking, photocleavable release
Click Chemistry Handles Alkyne, Azide (N3), DBCO, DBCO-PEG4, TCO, Tetrazine (TZ) Selective, aqueous-phase labeling without side reactions
Fluorophores FAM, HEX, TET, Cy3, Cy3.5, Cy5, Cy5.5, Cy7, TAMRA, ROX, Texas Red, ATTO dyes qPCR, FISH, smFRET, & sequencing detection assays
Quenchers & Non-Fluorescent Labels BHQ-1, BHQ-2, BHQ-3, DABCYL, Eclipse, MGB (Minor Groove Binder), DNP Fluorescence quenching, duplex stabilization (MGB), hybridization specificity
Polymer Conjugation PEGylation (PEG3, PEG4, PEG6, PEG12, PEG24, linear/branched PEG) In vivo stability, solubility, reduced renal clearance

Years Experience

Employees

Oligo Capacity (MT/yr)

GMP Faclities

Oligo Quality Tests

We provide all in-house release testing for typical GMP- and research-grade product specifications.

Category Method Instrument Test Description & Purpose
Appearance Visual Appearance N/A Evaluates color, clarity, and physical state of the solution or lyophilized powder.
General Properties pH (1% w/v solution) Mettler Toledo S470-K/S400-K Measures acidity/alkalinity to confirm formulation stability and compatibility.
Osmolality YASN Osmo210 Determines solute concentration to ensure isotonicity for biological applications.
Water Determination Mettler Toledo C30 Karl Fischer titration to quantify residual moisture content in solid samples.
Identity Single-strand molecular mass by IPRP-MS Waters Acquity Premier / Xevo G3 QTof Accurate mass verification of full-length single-stranded oligonucleotides.
Tm by UV spectroscopy Thermo E201 Determines melting temperature to assess duplex thermal stability and hybridization.
Sequencing by MS/MS Waters Acquity Premier / Xevo G3 QTof Tandem mass spectrometry fragmentation to confirm primary nucleotide sequence.
Duplex retention time Agilent 1260/1290, Waters Acquity Premier Chromatographic profiling to verify duplex formation and hybridization integrity.
Counter Ions Sodium content by IC Thermo ICS 6000 Ion chromatography quantification of sodium salt form counter-ions.
Assay UV absorption (anhydrous) Thermo E201, NanoDrop Spectrophotometric quantification of active oligonucleotide content at 260 nm.
Purity Non-denaturing IPRP-HPLC-UV Waters Acquity Premier, QTof G3 Assesses intact secondary structure purity and native double-strand percentage.
Denaturing AEX-HPLC UV Waters Acquity Premier, QTof G3 Anion-exchange separation resolving full-length product from short-mer failure sequences.
Denaturing IPRP-HPLC UV Waters Acquity Premier, QTof G3 Ion-pair reversed-phase resolution of lipophilic impurities and modified variants.
Process Impurities Residual solvents (GC-FID) Agilent 8890B GC Gas chromatography profiling to ensure organic solvent levels meet ICH limits.
Elemental impurities (ICP-MS) Thermo iCAP RQ Trace heavy metal analysis (e.g., Pd, As, Cd, Pb) via plasma mass spectrometry.
Safety Bacterial endotoxins Microplate Reader LAL assay detection to confirm pyrogen-free status for biological safety.
Safety Bioburden Microplate Reader Quantitative microbial enumeration test ensuring sterility standards.