Custom siRNA synthesis at 1000 g+ scale — advanced chemistry, stereodefined control, and delivery-ready conjugation.
Looking for standard DNA/RNA synthesis? See Custom DNA & RNA Oligo Synthesis Services.
Bio-Synthesis supports custom siRNA synthesis and RNA interference (RNAi) [1,2] manufacturing programs from early feasibility through late-stage development by combining advanced oligonucleotide chemistry with scalable manufacturing. Our platform is built for pharmaceutical and biotechnology teams that require structural precision, reproducibility across scale, and the ability to engineer duplex architecture, backbone chemistry, and conjugation strategy.
Our largest program volume is custom siRNA synthesis, including flexible duplex designs beyond canonical formats, advanced backbone systems (including PN and PACE-type chemistries), and stereodefined control where required.
siRNA manufacturing platform
Architecture flexibility + advanced chemistries, executed with reproducibility across scale.
Scale
Per sequence support
Stereo
Stereodefined PS
Design
>27 nt + long overhangs
Backbone
Advanced architectures
Three core pillars that matter in therapeutic siRNA programs: architecture control, chemistry control, and reproducibility across scale.
Beyond 27 nt, extended 3′/5′ overhangs (short or long stretch), blunt ends, asymmetric duplexes, and position-specific patterns.
See duplex engineering →
Backbone engineering including PS/PS2, PN, and PACE-type chemistries, integrated with sugar/base libraries and conjugation-ready handles.
See backbone engineering →
Reproducible workflows designed for transition from early development to industrial-scale supply exceeding 1000 g per sequence.
See execution workflow →
Built for pharma & biotech
Architecture precision • Reproducibility • Scale readiness
Primary modality
siRNA synthesis
Custom duplex + chemistry control
Engagement
Development partner
From lead optimization to scale-up
RNA interference (RNAi) is a sequence-specific, post-transcriptional gene silencing pathway [1]. Therapeutic small interfering RNA (siRNA) [2] duplexes are delivered to cells and processed through the RNA-induced silencing complex (RISC). The guide strand is retained and directs RISC to complementary mRNA, enabling catalytic cleavage and reduced protein expression.
Suggested Figures
Optional visuals to help communicate mechanism, duplex formats, and stereochemistry to non-specialist stakeholders.
Figure 1: RNAi mechanism (siRNA → RISC loading → mRNA cleavage).
Figure 2: Duplex formats (canonical 21–23mer vs extended duplex >27 nt; long overhangs; asymmetric).
Figure 3: Stereochemistry concept (mixed PS vs stereodefined Rp/Sp PS).
For therapeutic programs, manufacturing must preserve molecular architecture and impurity control across scale to reduce development risk.
Our custom siRNA synthesis services support duplex architectures beyond canonical 21–23mer formats, including extended overhang designs, asymmetric strand placement, and position-specific chemical modification patterns.
Backbone chemistry directly influences nuclease resistance, protein binding, pharmacokinetics, and tolerability. We support advanced backbone architectures for therapeutic programs, including phosphorothioate systems, phosphoramidate chemistries, and non-ionic backbones.
Explore the full catalog of phosphate, phosphorothioate, phosphoramidate, non-ionic, and hybrid backbone systems with position-specific incorporation options.
Backbone chemistries may be incorporated in fully modified architectures or mixed patterns with position-specific control to support potency, stability, and safety objectives.
Phosphorothioate and related backbone linkages introduce chirality at the phosphorus center, resulting in Rp and Sp diastereomers [3]. Conventional synthesis typically yields mixed stereochemical populations.
Stereodefined patterns are implemented only where appropriate for program objectives and analytical strategy.
Sugar and base chemistry are primary levers for tuning nuclease resistance, affinity/duplex stability, potency, and innate immune activation. We support extensive libraries with base- and position-specific incorporation.
For detailed modification catalogs (including base-resolved variants and conjugation handles), request a technical capability package.
Conjugation strategies are commonly used to tune biodistribution, exposure, and tissue uptake [4,5]. We support site-specific conjugation and scalable manufacturing workflows for lipid, peptide, ligand, and antibody-directed siRNA delivery platforms.
Cholesterol (3′/5′), fatty acids across a broad carbon range, and custom hydrophobic tails compatible with scalable manufacturing.
Explore →
Mono- and multivalent GalNAc architectures for hepatocyte targeting workflows.
NHS and other activated handles; custom ligands and program-specific conjugation strategies evaluated upon request.
Site-specific conjugation of functional peptides including cell-penetrating peptides (CPPs), receptor-binding peptides, and endosomal escape motifs to support cellular uptake and tissue targeting strategies.
Ligand-directed siRNA conjugates designed for receptor-mediated uptake, including small-molecule ligands, vitamins, carbohydrates, and custom targeting motifs.
Antibody-directed siRNA conjugation strategies supporting targeted delivery platforms, including linker-enabled and site-specific conjugation workflows evaluated per program.
A structured development-to-supply workflow designed to preserve molecular architecture, stereochemical integrity, and reproducibility across scale.
Duplex length, overhang design, backbone system (PS/PN/PACE), stereochemical pattern, and conjugation strategy defined upfront.
Scalable solid-phase synthesis with purification strategy aligned to required purity profile and projected manufacturing scale.
LC-MS confirmation, impurity profiling, and modification verification with program-aligned analytical review.
Iterative refinement of stereochemistry, backbone patterning, and conjugation tuning for potency and PK objectives.
Process translation from development quantities to industrial-scale production exceeding 1000 g per sequence.
Controlled specifications, documentation alignment, and batch-to-batch reproducibility support.
We provide scalable manufacturing from discovery quantities through late-stage development with programs that require industrial-scale production exceeding 1000 grams per sequence.
We collaborate with pharmaceutical and biotechnology partners to reduce development risk by aligning chemistry decisions with scalable manufacturing.
Backbone and stereochemical variants to support SAR campaigns and candidate selection.
Process translation planning across scale with impurity and reproducibility focus.
CONTACT
Share target, sequence(s), duplex architecture requirements (length, overhangs), backbone/sugar chemistry, conjugation needs, purity, and scale. We’ll recommend a practical manufacturing + QC strategy and provide a quote.
Tip: For multi-sequence programs, share a list plus common specifications (purity, scale, modification patterns) to speed quoting.
Yes. We support flexible duplex formats including designs beyond 27 nt, extended overhang architectures, blunt ends, asymmetric duplexes, and position-specific chemistry patterns.
Yes. Backbone options include PS/PS2, PN, PACE-type phosphoramidate chemistry, vinylphosphonate, methylphosphonate, morpholino and related systems, as well as mixed architectures.
Phosphorothioate linkages create Rp/Sp diastereomers. Stereodefined synthesis enables controlled stereochemical incorporation rather than a mixed stereoisomer population.
Yes. We support lipid and targeting ligand conjugation strategies (including GalNAc formats) and can evaluate program-specific conjugation workflows.
We support scalable manufacturing from early development through industrial-scale production exceeding 1000 grams per sequence.
Yes. We provide detailed capability packages that include base-resolved and conjugation-ready variants upon request.
Selected foundational and translational publications relevant to RNA interference, siRNA chemistry, backbone engineering, and targeted delivery.
Inline citations on this page refer to the numbered items above.
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