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Antisense LNA™ GapmeR

LNA™ GapmeRs are highly effective antisense oligonucleotides for knockdown of mRNA and lncRNA. Designed using advanced algorithms, the RNase H-activating LNA™ gapmers offer excellent performance and high success rate.

*50% discount on ExiLERATE LNA™ qPCR primer sets purchased with Antisense LNA™ GapmeRs

Discount is valid on orders received by 30 September 2017. Order must include at least one Antisense LNA™ GapmeR. 50% discount applies to ExiLERATE LNA™ qPCR primer sets and Control primer sets (309999, 309998, 308000-3080XX). Please mention the promo code VALIDATE50 when ordering. Discount may not be combined with any other offer. Discount valid only in regions where Exiqon offers direct sales. In countries where Exiqon uses distributors, please contact your distributor.
  • Highly potent single-stranded antisense oligonucleotides (ASO) for silencing of lncRNA and mRNA
  • Function by RNase H dependent degradation of complementary RNA targets
  • 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 transfection reagents
  • Designed with sophisticated and empirically developed algorithm
  • Available in individual tubes or custom 96-well plates for convenient screening

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

Exiqon LNA™ GapmeRs are powerful tools for loss of function studies of proteins, mRNA and lncRNAs. These single strand antisense oligonucleotides catalyze RNase H-dependent degradation of complementary RNA targets. Exiqon LNA™ GapmeRs are 16 nucleotides long enriched with LNA™ in the flanking regions and DNA in a LNA™ free central gap - hence the name GapmeR (Figure 1). The LNA™-containing flanking regions confer nuclease resistance to the antisense oligo while at the same time increase target binding affinity regardless of the GC content. The central DNA “gap” activates RNase H cleavage of the target RNA upon binding. LNA™ GapmeRs have fully modified phosphorothioated (PS) backbones which ensure exceptional resistance to enzymatic degradation.

Sophisticated online design tool

LNA™ GapmeRs are designed using empirically derived design tool that incorporates our more than 20 years of experience with LNA™ design. For each RNA target the tool evaluates thousands of possible LNA™ GapmeR designs against >30 design parameters and identify LNA™ GapmeRs most likely to give potent and specific target knockdown.

The primary design parameters are:
  • 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 for selection of the most specific LNA™ GapmeRs with minimal off-targets in the spliced and unspliced transcriptomes
  • Optimal oligonucleotide design. Length, Tm, gap size, self-complementarity, LNA™ positions etc.
Enter the sequence of your RNA target and our online tool will design your LNA™ GapmeRs ready to order. You can also submit your RNA sequence and let our technical support handle the design for you.

Table 1 Workflow for Antisense LNA™ GapmeRs
Workflow for Antisense LNA™ GapmeRs. (Click to learn more)

Coverage

Antisense LNA™ GapmeRs can be designed for any RNA target >80 nucleotides and are available in five different categories depending on application (see also
s 1 & 2):

  • Antisense LNA™ GapmeRs in vitro Standard: Cost effective LNA™ GapmeRs in tubes for initial testing of multiple designs using standard cell-lines.
  • Antisense LNA™ GapmeR in vitro Premium: HPLC-purified LNA™ GapmeRs with guaranteed purity sui
    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 that have in vivo testing as the ultimate goal. Also recommended for hard-to-transfect cell-lines such as B-cells, primary cell lines, cells in suspension etc.
  • Custom Antisense LNA™ GapmeR in vivo Large Scale: The same high quality and purity as the in vivo Ready LNA™ GapmeRs available with custom large scale yields.
  • Antisense LNA™ GapmeR custom plates: In vitro Standard LNA™ GapmeRs delivered in convenient 96-well plate format for screening projects (Figure 2). Learn more.
Antisense LNA™ GapmeRs can be delivered in larger yields and with other modifications. Please contact us for more information.

Antisense LNA™ GapmeR custom plates and Custom LNA™ GapmeRs for in vivo use are custom products. Please contact us for information and ordering.

Table 2 Overview of Antisense LNA™ GapmeR products
Overview of Antisense LNA™ GapmeR products. (Click to learn more)

Figure 1 Structure and function of the LNA™ longRNA GapmeRs
Structure and function of the Antisense LNA™ GapmeRs. (Click to learn more)

Figure 2 Custom plates with LNA™ GapmeRs for RNA functional analysis screening projects
Custom plates with LNA™ GapmeRs for RNA functional analysis screening projects. (Click to learn more)

Potent knockdown of mRNA

The efficacy of mRNA knockdown (KD) with LNA™ GapmeRs rivals that of siRNA (Figure 1). LNA™ GapmeRs are therefore an excellent alternative for researchers looking for a method that works independently of RISC and has no microRNA-like off-target effects.

Ideal for knockdown of lncRNA

Loss of function analysis of lncRNA can be particularly challenging for several reasons. Many lncRNAs are involved in transcriptional regulation by attracting chromatin modifying enzymes to certain DNA targets. Confined to the nuclear compartment these lncRNAs are inefficiently targeted by siRNA. In contrast, nuclear retained RNAs are particularly sensitive to LNA™ GapmeRs exactly because they share the nuclear compartment with RNaseH, the endonuclease responsible for LNA™ GapmeR activity (Figure 2-5). In addition, lncRNAs often derive from transcriptionally complex loci with overlapping sense and antisense transcripts. Strand-specific knockdown is therefore of crucial importance which is guaranteed with LNA™ GapmeRs because they are single stranded. Figure 4 displays examples of effective knockdown of various lncRNA regardless of their intracellular localization.

No transfection reagent needed

Due to their small size and exceptional potency and stability, LNA™ GapmeRs are taken up efficiently by cells directly from the culture medium. With many cell lines potent knockdown of target RNA is therefore achievable with unassisted delivery (Figure 5) – avoiding the confounding cytotoxic effects normally associated with transfection reagents. However, non-assisted uptake does require higher concentrations of LNA™ GapmeR than is necessary with lipid-based transfection and the knockdown kinetics are slower. Usually knockdown is observed only after 48 h of culturing in the presence of the LNA™ GapmeR.

RNA functional analysis screening projects

Custom plates of LNA™ GapmeRs are being used for screening projects to identify RNA functions important for particular biological processes or diseases. Biogazelle chose LNA™ GapmeRs as their preferred technology for screening lncRNA cancer therapeutic targets after comparing the performance of 200 LNA™ GapmeRs alongside other platforms. Read more.

Study RNA function in live animal models

Excellent pharmacokinetic and pharmacodynamic properties of LNA™ GapmeRs have been demonstrated in many different tissues and organs. LNA™ antisense oligonucleotides are well tolerated and show low toxicity in vivo. In addition, short, high affinity LNA™ GapmeRs are active at lower concentrations compared to other antisense oligonucleotides. The incorporation of LNA™ increases the serum stability of the ASO.

LNA™ GapmeRs have also been shown to have high potential to penetrate the cell membrane barrier and successfully interact with intracellular and even nuclear retained targets. Effective and long lasting knockdown of mRNA and lncRNA can be achieved in a broad range of tissues with LNA™ GapmeRs administered in live animal models. Figure 6 shows in vivo knockdown of a highly abundant nuclear-retained lncRNA. In addition, specific formulation (e.g. liposomes or cationic complexes) is not required for efficient delivery in vivo, making the workflow easier.

Validate RNA Silencing by qPCR

ExiLERATE LNA™ qPCR assays are ideal for confirming knockdown of the RNA transcript of interest. ExiLERATE LNA™ qPCR assays designed to amplify precisely your transcript of interest can be conveniently purchased along with your LNA™ GapmeRs, and robust detection of any mRNA or lncRNA is guaranteed. Exiqon also offer a range of validated positive control LNA™ GapmeRs and corresponding validated ExiLERATE LNA™ qPCR Control primer sets, as well as primer sets for candidate reference genes to ensure accurate normalization of qPCR data. Read more in our Top 5 Tips for qPCR Validation of RNA Silencing.

Selected publications – Long noncoding RNA

Adriaens et al. Nat Med. 2016 Aug;22(8):861-8.
Leucci et al. Nature 2016, 531(7595): 518-22.
Viereck et al. Science Translational Medicine 2016, 8(326):326ra22.
Lin et al. Nat Cell Biol. 2016 Feb;18(2):213-24.
Michalik et al. Circ. Res. 2014, 114: 1389-97.
Xing et al. Cell 2014, 159: 1110-1125.
Figure 1 Structure of the Antisense LNA™ GapmeRs
Antisense LNA™ GapmeRs structure. (Click to learn more)

Figure 2 Structure and function of the Antisense LNA™ GapmeRs
Antisense LNA™ GapmeRs mode of action. (Click to learn more)

Figure 3 Antisense LNA™ GapmeR success rate
Antisense LNA™ GapmeR success rate. (Click to learn more)

Figure 4 Antisense LNA™ GapmeR examples
Antisense LNA™ GapmeR knockdown examples. (Click to learn more)

Figure 5 Antisense LNA™ GapmeR gymnosis LNA™ GapmeRs can be used without a transfection agent. (Click to learn more)

Figure 6 Antisense LNA™ GapmeR in vivo
In vivo knockdown using Antisense LNA™ GapmeRs. (Click to learn more)

Prof. Thomas Thum

Silencing the lncRNA Chast reverses cardiac disease


"Antisense LNA™ GapmeRs target the lncRNA directly and allowed us to test the therapeutic potential of Chast silencing in animal models."

Prof. Thomas Thum and Dr. Janika Viereck work at the Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Germany. They recently published a Science Translational Medicine paper on the lncRNA Chast and its involvement in cardiac remodelling.

Read full story...

Prof. Jean-Christophe Marine

Melanoma addiction to the long non-coding RNA SAMMSON


"We have been particularly impressed by the efficiency of targeting using Antisense LNA™ GapmeRs In vivo and would recommend them for pre-clinical studies."

Prof. Jean-Christophe Marine and Dr. Eleonora Leucci work at the Laboratory for Molecular Cancer Biology, K.U. Leuven in Belgium. They recently published a Nature paper showing that melanoma cancer cells are addicted to the lncRNA SAMSSON.

Read full story...

Dr. Jaya Krishnan

Silencing eRNA – towards novel therapeutics for heart disease


"The hypertension protocol gave us the most exciting and elegant data in vivo....We used LNA™ GapmeRs is because it's fairly straightforward and we can use some of the established [in vivo] protocols."

Dr. Jaya Krishnan is a group leader at the MRC Clinical Sciences Centre and Imperial College London, UK.

Read full story...

Prof. Antony Cooper

Long non-coding RNAs and Parkinson's Disease


"LNA™ GapmeRs clearly gave us better results than the other approaches that we tried, and that is all that matters."

Assoc. Prof. Antony Cooper is the divisional head of Neuroscience in the Garvan Institute of Medical Research (Sydney, Australia). His lab's research focuses on the area of neurodegenerative disease, and specifically understanding the basis of Parkinson's Disease.

Read full story...

Dr. Eugenia de la Morena-Barrio

Identifying new prognostic markers and treatment approaches for thrombosis


"I am really happy with the degree of silencing I have obtained with GapmeRs technology. The main benefit of Exiqon LNA™ GapmeRs is that you can obtain a very high silencing degree of your interest gene and that this silencing is quite reproducible in different cell lines."

Dr. Eugenia de la Morena-Barrio is a postdoc at the Department of Internal Medicine, University of Murcia, Spain. Her group has been using LNA™ GapmeRs to silence two different cell lines which are involved in the risk of developing thrombosis, to identify new prognostic markers and developing new treatment approaches.

Read full story...

Rudi Micheletti

The role of long non-coding RNAs in the heart


"GapmeR knock down was reproducible and specific to my target. The percentage of GapmeRs able to knock down the specific target was impressively high."

Rudi Micheletti works at the Centre Hospitalier Universitaire Vaudois in Switzerland. He has been using Exiqon's LNA™ GapmeRs to identify and characterize long non-coding RNAs involved in the response of the heart to stress.

Read full story...

Anastasia Khvorova

Silencing of genes linked to neurodegenerative diseases


"Overall we obtained a very good hit rate – all but one of the LNA™ GapmeRs did knockdown the target mRNA and several of the LNA™ GapmeRs were extremely potent with IC50s of around 25 nM."

Anastasia Khvorova works at the RNA Therapeutics Institute at the University of Massachusetts Medical School. Her lab has been using LNA™ GapmeRs to silence two different genes which are valid therapeutic targets for neurodegenerative diseases.

Read full story...

Dr. Jean-Christophe Marine

Inhibition of long noncoding RNAs using LNA™ longRNA GapmeR


"LNA™ gapmers allow efficient targeting of lncRNAs which can be difficult to target by other technologies such as siRNA/shRNA."

Drs. Jean-Christophe Marine, Eleonora Leucci and Laura Standaert work at the Laboratory for Molecular Cancer Biology, K.U. Leuven in Belgium. They have been using LNA™ longRNA GapmeRs to silence non-coding RNAs linked to cancer.

Read full story...

Dr. Reinier Boon

Long non-coding RNAs in the cardiovascular system


"It is currently the best tool to knock down lncRNAs in vivo."

Drs. Reinier Boon, Stefanie Dimmelerand and Katharina Michalik work at the Institute for Cardiovascular Regeneration at the Goethe University in Frankfurt, Germany. They are interested in microRNAs and long non-coding RNAs (lncRNAs) that control cardiovascular functions in endothelial cells.

Read full story...

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