Engineer oligonucleotides for nuclease resistance and hybridization stability using stabilizer bases, 2′‑sugar chemistries (2′‑OMe, 2′‑F, MOE, LNA), and backbone controls (PS, end‑caps, spacers). From screening to RUO → GMP‑like, Bio‑Synthesis provides HPLC/PAGE, optional LC‑MS, ISO‑aligned docs, and tech transfer.
Bio-Synthesis Inc. engineers oligonucleotides for nuclease resistance and hybridization stability using a toolkit of stabilizer bases, 2′-sugar chemistries (2′-OMe, 2′-F, MOE, LNA) and backbone controls (phosphorothioate, terminal caps, spacers). We help you balance potency and protection—tuning Tm, enzyme compatibility, and off-target risk—from screening to RUO → GMP-like manufacturing with HPLC/PAGE and optional LC-MS, ISO-aligned documentation, and tech transfer support.
Base analogs are best used alongside sugar/backbone changes for robust nuclease resistance.
Gapmer (RNase H) and steric-blocker ASOs with PS/LNA/2′-mod sugar mixmers; RUO→GMP-like docs.
21-mer duplexes with 2′-OMe/2′-F and terminal PS for nuclease control; UU/dTdT overhangs.
SELEX-derived motifs stabilized with selective 2′-mods/PS; functionalized with biotin, dyes, PEG, lipids.
Neutral phosphorodiamidate morpholino backbone—enzyme-proof scaffolds for splice-modulating ASOs.
Peptide-like backbone with ultra-strong binding; ideal for diagnostics and clamps; benefits from conjugation.
DNA core for RNase H recruitment with 2′-modified wings for stability and PK.
We combine base, sugar, and backbone strategies—universal bases where appropriate—with controlled phosphorothioate (PS) patterning, 2′‑OMe/2′‑F/LNA placement, end‑caps, and spacers to improve nuclease resistance while maintaining activity.
dI • 5NI • 3NP • K-Base 2′-OMe, 2′-F, LNA PS pattern & end-caps
Limit consecutive universals Buffer Tm locally Polymerase constraints
HPLC/PAGE • LC-MS (opt.) Format & labeling Docs & QC package
Serum/lysate tests Compare layouts Scale/transfer
Typical ASO gapmer: PS backbone throughout; 2′-MOE/2′-OMe/LNA in wings; DNA core for RNase H recruitment. Mixmer probes use LNA/BNA for affinity and 2′-OMe for stability.
High LNA content raises affinity; manage off-target risk via shorter wings and sequence screens. PS stereochemistry can affect protein binding; consider stereo-defined designs.
Adjust stringency (formamide/salt) for high-affinity chemistries; validate melting profiles; protect fluorophores during stability testing.
Two common ASO archetypes. Start here, then tune %LNA/2′-mods and PS patterning to balance potency, off-targets, and PK.
Baseline duplex with stability and safety tweaks. Adjust modification density by matrix (serum/lysate/cell) and delivery route.
RNase H–competent ASO: high-affinity 2′-modified wings protect the ends; a DNA core recruits RNase H. Tune %LNA/2′-mods and PS patterning.
Start with a validated/SELEX motif; then stabilize, truncate, and format for use. Buffer (Mg2+/K+) and folding conditions are critical.
A function/property. It is achieved by applying specific modification types (e.g., 2′-mod sugars, PS backbones, PMO/PNA).
Start with a PS backbone + 2′-OMe/MOE/LNA wings (gapmer). Tune LNA content to manage off-targets and maintain potency.
Use when maximum nuclease resistance and neutrality are required (e.g., in vivo delivery studies). Consider conjugation for uptake.
BNA (bridged nucleic acid) refers to LNA-like chemistries (e.g., cEt, ENA, AmNA) that pre-organize the ribose for higher affinity and nuclease resistance. They offer LNA-class stability with tunable safety profiles.
A morpholino-class backbone variant incorporating thio features; like PMO, it is neutral and highly nuclease-resistant. It’s explored for splice modulation and delivery conjugation strategies.
Yes. We support bench to multi-gram with phase-appropriate documentation and QC, and we can prepare tech-transfer packages for GMP-like manufacturing.
We can discuss stereo-enriched or defined PS strategies on request, balancing potency, off-target protein binding, and manufacturability.
Both are enzyme-proof. PMO is widely used for splice-modulating ASOs; PNA shows ultra-strong binding but often benefits from delivery conjugates.
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