Antisense LNA GapmeRs

• Function by RNase H-dependent degradation of complementary RNA targets
• Provide strand-specific knockdown with no RISC-associated off-target activity
• Active in vivo and in vitro, enabling the analysis RNA function in a wide range of model systems
• Excellent alternative to siRNA for knockdown of mRNA and lncRNA
• Taken up by cells without need for transfection reagents
• Variety of controls support transfection or unassisted uptake protocol optimization

Antisense LNA GapmeRs are highly potent, single-stranded antisense oligonucleotides (ASO) for silencing of lncRNA and mRNA in cell cultures and even in animal models. Antisense LNA GapmeR Positive Controls enable optimization of conditions for lipid-based transfection, electroporation or unassisted delivery. The GapmeRs are enhanced with LNA technology and are designed using sophisticated and empirically developed algorithms and offer excellent performance and high success rates.
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Potent knockdown of mRNA or lncRNA

Tool-of-choice for silencing of lncRNA

No transfection reagent needed

Potent positive controls with optimal specificity

Study RNA function in live animal models

Efficient silencing of mRNA and lncRNA with fewer off-target effects

Antisense LNA GapmeRs are powerful tools for protein, mRNA and lncRNA loss-of-function studies. These single-stranded, antisense oligonucleotides (ASOs) catalyze RNase H-dependent degradation of complementary RNA targets. The Antisense LNA GapmeRs are 16 nucleotides long and are enriched with LNA in the flanking regions and DNA in an LNA-free central gap, hence the name "GapmeR" (see figure  A unique short, single-stranded antisense design). The LNA-containing flanking regions confer nuclease resistance to the antisense oligo, while also increasing target binding affinity, regardless of the GC content. The central DNA "gap" activates RNase H cleavage of the target RNA upon binding. Antisense LNA GapmeRs have fully modified phosphorothioate (PS) backbones, which ensure exceptional resistance to enzymatic degradation.

Sophisticated design parameters

Antisense LNA GapmeRs are designed using our empirically derived design tool that incorporates more than 20 years of experience with LNA design. For each RNA target, the tool evaluates thousands of possible designs against more than 30 design parameters to identify the Antisense LNA GapmeRs most likely to provide potent and specific target knockdown.
The primary design parameters include the following:

• Optimal target sequence accessibility to ensure high potency. The design tool selects target sequences based on local secondary structure prediction.
• Antisense off-target evaluation. GapmeR sequences are aligned against ENSEMBL to enable selection of the most specific Antisense LNA GapmeRs with minimal off-targets in the spliced and unspliced transcriptomes.
• Optimal oligonucleotide design, including length, T_m, gap size, self-complementarity, LNA positions, etc.

Coverage

Antisense LNA GapmeRs can be designed for any RNA target >80 nucleotides and are available in several different grades, depending on your application:

• Antisense LNA GapmeR Standard: cost-effective LNA GapmeRs in tubes for initial testing of multiple designs using standard cell lines.
• Antisense LNA GapmeR Premium: HPLC-purified LNA GapmeRs with guaranteed purity suited for most cell assays; also available with 5’ or 3’ fluorescent labels.
• Antisense LNA GapmeR in vivo Ready: high-quality, animal-grade LNA GapmeRs recommended for any projects with in vivo testing as the ultimate goal. Also recommended for difficult-to-transfect cell lines, such as B cells, primary cell lines, cells in suspension, etc.
• Antisense LNA GapmeR in vivo Large Scale: high-quality, animal-grade LNA GapmeRs available in a range of scales with various purification and labeling options.
• Antisense LNA GapmeR Custom Plates: Standard LNA GapmeRs delivered in convenient 96-well plate format for screening projects.

Highly purified Antisense LNA GapmeRs for in vivo studies

We also offer higher-purity Antisense LNA GapmeRs for use in in vivo studies. These Antisense LNA GapmeRs have excellent pharmacokinetic and pharmacodynamic properties and offer effective and long-lasting RNA silencing in a broad range of tissues. They are well-tolerated and show low toxicity in vivo, due to the following unique features:

• High target affinity: LNA nucleotides positioned at the extremities increase affinity for the target.
• Excellent stability: the combination of LNA nucleotides and phosphorothioate backbone modifications lead to high stability. The LNA GapmeRs are highly resistant to nucleases and have a long half-life in serum.
• Short length: LNA modifications enable design of short (15–16mer) gapmers with high target affinity. This is much shorter than conventional gapmers, which are typically around 20 nucleotides long. Shorter oligonucleotides are generally taken up much more efficiently via natural cellular uptake mechanisms, so Antisense LNA GapmeRs are highly effective in live animal models. Short oligonucleotides are also less prone lead to toxicity from binding proteins, such as Toll-like receptors and components of the complement system.
• Excellent biodistribution: oligonucleotides with standard phosphodiester backbones are lost into the urine. However, PS-modified oligonucleotides bind with albumin in the bloodstream. This extensive but low-affinity binding helps prevent loss of PS-modified oligonucleotides by renal filtration and facilitates rapid uptake in a broad range of tissues.