Antisense oligonucleotides are short, chemically modified single-stranded nucleic acids that bind a target RNA and silence it, alter its splicing or mark it for degradation. For a research lab they are a custom synthesis purchase like any oligo, but the chemistry is heavier: phosphorothioate backbones, modified sugars, sometimes a gapmer design with different chemistry in the middle and at the ends. Those modifications are what make the molecule work in a cell and what make the price list look different from a primer's. This page covers the choices for research-use antisense oligonucleotides and points at the vendor comparison.
Why the chemistry is the price
An unmodified oligo is degraded in serum and inside cells within minutes. Antisense oligonucleotides therefore carry a phosphorothioate backbone throughout and sugar modifications such as 2'-O-methoxyethyl, 2'-O-methyl or locked nucleic acid bases at the ends. Each modified phosphoramidite is a distinct, more expensive reagent, coupling is slower, and the full-length product must be purified away from a larger population of failure sequences. A quote for an antisense oligonucleotide is a quote for that chemistry, and vendors differ widely in which modifications they offer and at what scale.
Gapmers, steric blockers and what to specify
A gapmer has a central stretch of unmodified deoxynucleotides flanked by modified wings and recruits an enzyme to cut the target; a fully modified steric blocker binds without cutting and is used to redirect splicing or block a binding site. The design decides which positions carry which chemistry, so the order form is a position-by-position specification rather than a sequence and a tick box. Write the design out explicitly and confirm with the vendor that every position is achievable at your scale before you compare prices.
Purification, analysis and delivery
HPLC purification is the norm, and for anything going into animals a mass spectrometry report on identity and a purity figure on the certificate are the minimum. Ask for endotoxin testing and sterile filtration if the oligo will be dosed in vivo, and ask how it will be delivered: dry, or in a stated buffer at a stated concentration. Vendors price these as separate lines and a low headline price often excludes them.
Comparing vendors for research-use antisense synthesis
The oligo pages on this site record what each synthesis vendor publishes for custom synthesis by scale and grade, verified on the vendor's own page and dated. Use them to shortlist vendors who publish modified oligo pricing at all, then send the identical specification to each. The comparison is for research-use material; a therapeutic candidate moves to a manufacturer under a quality system and a different contract.
phosphorothioate oligonucleotides, and what the backbone buys
A phosphorothioate substitutes one non-bridging oxygen in the backbone for sulfur, and that single change is why antisense chemistry works in a living system: nucleases cut the natural linkage in minutes, and the modified one survives long enough to reach a target. It also increases protein binding, which lengthens circulation and drives much of the class toxicology, and it introduces a stereocentre at every modified linkage, so a fully substituted strand is a mixture of diastereomers unless the synthesis controls it. Specify the substitution pattern and the purity method, because the two decide most of the price of a modified oligonucleotide.
modified oligonucleotides, and what each modification buys
Backbone, sugar and base modifications each solve a different problem. Phosphorothioate linkages resist nucleases and raise protein binding, which lengthens circulation and carries much of the class toxicology. Two prime O-methyl and two prime fluoro sugars raise affinity and stability; locked nucleic acids raise it further and can self-structure. Base modifications tune melting and immune recognition. A therapeutic strand is a pattern of all three rather than one choice, and a research order states the pattern position by position.
oligonucleotide purification and what each grade gives
oligonucleotide purification runs from desalting, which removes salts and nothing else, through cartridge purification to full chromatography, and the grade needed follows the application rather than the length: a sequencing primer tolerates desalting while a probe or a therapeutic candidate does not. Full length content rather than purity by absorbance is the specification that matters.
A c3 spacer and what a spacer does
A c3 spacer is a three carbon insert used to block polymerase extension, to hold a modification away from the duplex, or to break a sequence without changing its length, and because it blocks extension it is the standard three prime terminator on a probe. Its position rather than its chemistry is what a design has to state.
Questions people ask about antisense oligonucleotides
What are antisense oligonucleotides used for in research?
To knock down a transcript, to alter splicing of a target, to block a microRNA or a protein binding site on an RNA, and as tool compounds in animal models.
What is a gapmer?
An antisense design with a central deoxynucleotide gap flanked by chemically modified wings; the gap recruits RNase H to cut the bound target while the wings raise affinity and stability.
Why are antisense oligonucleotides more expensive than primers?
Every position carries a modified backbone and often a modified sugar, each a more expensive reagent with slower coupling, and the product needs HPLC purification and analytical release.
Can I order antisense oligonucleotides for animal studies?
Yes from research-use vendors, with HPLC purification, mass spectrometry, endotoxin testing and sterile formulation specified on the order.