Chemically modified siRNA provides a flexible way to tune RNA interference experiments when unmodified duplexes do not provide the required stability, specificity, handling properties, or compatibility with downstream delivery systems. Strategic changes to the ribose, phosphate backbone, nucleobases, and terminal groups can alter nuclease resistance, duplex behavior, strand selection, off-target potential, and conjugation readiness. Successful modification therefore depends not only on selecting a chemistry, but also on deciding which strand and nucleotide positions should carry each modification.
Our chemically modified siRNA services combine sequence review, modification-pattern design, custom strand synthesis, purification, duplex formation, analytical characterization, and optional functional assessment. We support research teams developing modified siRNA for gene-silencing studies, target validation, stability-sensitive experiments, delivery research, and structure-function investigations. Projects can start from an existing siRNA sequence or include coordinated support through our siRNA design services.
Modification Placement vs. RNAi Activity: A chemistry that improves stability can still reduce silencing if it is placed at a position important for guide-strand recognition, target pairing, or RISC-mediated cleavage. We evaluate guide and passenger strands separately and develop position-aware modification patterns rather than applying the same chemistry indiscriminately across the duplex.
Nuclease Resistance vs. Duplex Function: Unmodified RNA can be vulnerable to degradation, while excessive modification may change duplex thermodynamics or interfere with productive RNAi processing. Ribose and backbone modifications are selected and distributed to improve resistance while preserving the structural features required for the intended gene-silencing experiment.
Strand Bias and Off-Target Effects: Unwanted passenger-strand loading and seed-mediated interactions can complicate phenotype interpretation. Asymmetric modification patterns, selective passenger-strand modification, and carefully positioned guide-strand changes can be considered together with sequence design to improve experimental specificity.
Complex Synthesis and Duplex Quality: Multiple internal modifications, terminal functionalities, or conjugates increase synthesis and purification complexity. Each strand must be produced and characterized individually before controlled annealing, because impurities or incorrect strand ratios can affect the quality and reproducibility of the final siRNA duplex.
Compatibility With Delivery Systems: Chemical modification cannot be planned independently of delivery. Cholesterol, targeting ligands, peptides, nanoparticles, and other delivery formats may change siRNA hydrophobicity, steric environment, cellular uptake, and intracellular availability. Our RNA delivery capabilities can be considered during chemistry planning when the project requires delivery-oriented research.
Our service model is designed for projects in which the modification pattern must be matched to a specific experimental objective rather than selected from a generic list. We can work from customer-provided sequences or integrate design, chemistry, synthesis, purification, analytical review, and downstream research support into one coordinated workflow.
Modification feasibility is assessed in the context of sequence composition, strand function, number and position of modified residues, terminal requirements, purification complexity, conjugation plans, and intended assay conditions. This approach helps research teams select practical chemistries while preserving the biological function expected from the siRNA duplex.
| Cat No. | Modification | Quantity | Purification | Price | Lead Time | |
| BRD-001 | Deoxyinosine | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-002 | 2'-Fluoro-rU | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-003 | 2'-Fluoro-rC | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-004 | 5'-Bromo-rU | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-005 | 2'-OMe-rU | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-006 | 2'-OMe-rC | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-007 | 2'-OMe-rG | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-008 | 2'-OMe-rA | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-009 | 5'-Phosphate | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-010 | 3'-Phosphate | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-011 | 5'-Amine | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-012 | 3'-Amine | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-013 | 5'-Biotin | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-014 | 3'-Biotin | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-015 | 5'-Thiol | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-016 | 3'-Thiol | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-017 | 5'-Digoxigenin | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-018 | 3'-Digoxigenin | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-019 | Spacer C3 | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-020 | Spacer C6 | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-021 | Spacer 9 | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-022 | Spacer 18 | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-023 | 5'-Cholesterol | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-024 | 5'-Ferrocene | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-025 | 3'-Ferrocene | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-026 | 2'-Isoproply | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
| BRD-027 | phosphorothioates | 2 OD-250 OD | HPLC | Inquiry | Inquiry | |
Modification chemistry should be selected according to the specific weakness of the starting siRNA and the positions that can tolerate structural change. The matrix below summarizes common modification classes and the practical questions that should be considered before synthesis.
| Modification Class | Representative Options | Primary Design Purpose | Key Placement Considerations | Typical Research Use |
| 2'-O-Methyl Ribose | 2'-OMe-A, 2'-OMe-C, 2'-OMe-G, 2'-OMe-U | Improve nuclease resistance and tune recognition or off-target behavior | Modification density and location should be balanced against guide-strand function and target pairing | Stability-sensitive RNAi, specificity studies, modified duplex comparison |
| 2'-Fluoro Ribose | 2'-F pyrimidines and other feasible 2'-F configurations | Increase nuclease resistance while maintaining compact RNA-like duplex geometry | Affinity changes and modification position should be reviewed to preserve productive target recognition | Durable silencing studies, mixed 2'-OMe/2'-F patterns, stability optimization |
| Backbone Modification | Phosphorothioate and other project-dependent phosphate-linkage options | Improve resistance to exonucleolytic degradation and protect vulnerable termini | Excessive substitution may change duplex properties or nonspecific molecular interactions | Terminal stabilization, delivery-oriented constructs, stability comparisons |
| Base Modification | Deoxyinosine, 5-bromouridine, pseudouridine, selected base analogs | Adjust base-pairing behavior or introduce specialized chemical functionality | Target complementarity and local duplex structure should be assessed before substitution | Structure-function research, duplex-property studies, specialized assay development |
| Terminal Modification | Phosphate, amine, thiol, biotin, spacers and functional handles | Enable conjugation, immobilization, capture, labeling, or terminal protection | Guide-strand 5' chemistry and steric effects require particular attention | Conjugation studies, pull-down experiments, delivery research, analytical workflows |
| Delivery Conjugate | Cholesterol, GalNAc, peptide, polymer or nanoparticle-associated formats | Add delivery, targeting, uptake, or trafficking functionality | Attachment site, linker length, hydrophobicity and accessibility of the RNA duplex must be considered | Cellular uptake research, carrier comparison, targeted-delivery platform development |
Chemically modified siRNA development requires evaluation at both the single-strand and duplex levels. Sequence quality alone does not establish whether a construct is suitable for the intended experiment; modification placement, synthesis quality, annealing behavior, stability, and functional performance should be considered as connected development variables.
| Assessment Area | Objective | Typical Approach | Decision Supported | Project Stage |
| Sequence & Off-Target Review | Confirm that the starting duplex is suitable for modification | Target alignment, seed-region review, strand asymmetry assessment, sequence-context analysis | Whether sequence redesign should precede chemistry optimization | Design |
| Modification Geometry | Determine which positions can be modified without unnecessarily compromising RNAi function | Strand-by-strand mapping of ribose, backbone, base, and terminal changes | Final modification pattern and candidate set | Design |
| Strand Identity | Confirm that the intended modified oligonucleotide was synthesized | Mass-based identity assessment with sequence and calculated-mass review | Release of individual strands for duplex preparation | Synthesis / QC |
| Purity Assessment | Evaluate full-length material and synthesis-related impurities | Analytical chromatography following fit-for-purpose purification | Suitability for annealing and downstream experiments | Purification / QC |
| Duplex Formation | Confirm controlled assembly of complementary modified strands | Annealing-condition optimization, strand-ratio control, duplex integrity assessment | Final duplex preparation and experimental readiness | Assembly |
| Stability Assessment | Determine whether the modification pattern addresses the relevant degradation challenge | Comparative incubation or stability studies under project-relevant conditions | Selection among alternative chemistry patterns | Evaluation |
| Silencing Assessment | Verify that chemical modification has not eliminated useful RNAi activity | Target RNA or protein measurement after controlled siRNA treatment | Advancement of the preferred modified construct | Functional Validation |
| Delivery Compatibility | Determine whether chemistry, conjugate, and carrier operate as a compatible system | Uptake, formulation, carrier-comparison, or transfection optimization studies | Selection of an experimental delivery strategy | Application Development |
Our workflow connects modification design with practical oligonucleotide synthesis and downstream research requirements. Each stage is intended to reduce avoidable iteration by resolving sequence, chemistry, purification, duplex, and application questions before they become downstream experimental problems.
We review the target, siRNA sequence, experimental system, previous knockdown data, desired modification objective, quantity, format, and downstream assay. Defining whether the priority is stability, specificity, conjugation, strand control, or comparative chemistry testing establishes the technical basis for the project.
Guide and passenger strands are evaluated separately for sequence context, sensitive positions, modification compatibility, and synthesis feasibility. Existing sequences can be retained when appropriate, while problematic designs can be redirected for sequence optimization before material is produced.
Ribose, backbone, base, terminal, and conjugation modifications are mapped to defined positions. The project team reviews the proposed architecture, analytical requirements, purification strategy, and any reference or control duplexes before synthesis begins.
Modified sense and antisense strands are synthesized independently, deprotected, processed, and purified using methods selected for the chemistry involved. Individual-strand quality is assessed before the material is advanced to duplex preparation.
Complementary strands are combined under controlled annealing conditions and evaluated according to the agreed quality plan. Identity, purity, quantity, and duplex-related information are organized into a project-specific analytical package.
When requested, modified duplexes can progress into stability, delivery, transfection, or gene-silencing evaluation. Materials and data are then transferred with the relevant sequence, modification, and analytical information to support internal research review and subsequent experimental planning.
Chemically modified siRNA projects are most successful when modification chemistry, oligonucleotide synthesis, duplex quality, and intended biological use are planned as one system. Our service platform is structured around that integration, giving research teams practical support from modification selection through analytical and functional evaluation.
Modified siRNA is useful when the limitations of an unmodified duplex interfere with reliable gene-silencing experiments or when the siRNA must support additional chemical, analytical, or delivery functions. Our services can be adapted to both focused validation studies and broader RNAi platform-development programs.
Whether you need a simple 2'-O-methyl or 2'-fluoro substitution, terminal phosphorothioate protection, a multifunctional siRNA conjugate, or a position-specific mixed-modification pattern, our team can help translate the experimental objective into a practical synthesis and evaluation plan. Share your target, siRNA sequence, preferred modifications, desired quantity, downstream assay, and any stability or delivery challenges already observed. We can review the chemistry, identify key design risks, recommend an appropriate purification and analytical strategy, and coordinate optional downstream testing. Contact us to discuss your chemically modified siRNA requirements.
Common options include 2'-O-methyl, 2'-fluoro, phosphorothioate linkages, selected base modifications, terminal phosphates, amines, thiols, biotin, spacers, and delivery-related conjugates.
The choice depends on the required nuclease resistance, duplex behavior, modification position, target sequence, and desired RNAi activity. Mixed 2'-OMe/2'-F patterns may also be evaluated.
Yes. Guide-strand recognition, seed-mediated interactions, central target pairing, termini, and passenger-strand behavior have different structural requirements, so modification placement should be position specific.
Yes, compatible chemistries can be combined in one duplex. The number and positions of modifications should be reviewed together to avoid unnecessarily disrupting RNAi function.
Certain position-specific modifications can help reduce unwanted seed-mediated or passenger-strand activity, but chemical modification should be combined with appropriate sequence selection and experimental controls.
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