Custom LNA™ Antisense Oligonucleotides  Use LNA™ antisense oligonucleotides for your antisense inhibition experiments. Whether you choose mixmers or some other design, LNA™-enhanced oligonucleotides offer the high affinity needed for successful knockdown experiments.
Ina K. Dahlsveen, Ph.D., Product Manager | |
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- Superior sensitivity and specificity compared to traditional antisense oligonucleotides
- Designed using proprietary algorithms developed by Exiqon’s LNA™ experts
- Long lasting effect
- Available for a wide range of experiments
Features LNA™ oligonucleotides bind their complementary sequences with much higher affinity than either DNA or RNA oligonucleotides. This makes LNA™ oligonucleotides ideal for antisense knockdown applications. For examples on how LNA™ knockdown oligonucleotides have been used, click the Experimental data tab above.
You can choose to design your own oligonucleotides or let us do the work. If you choose to do your own designs, please see our design guidelines at the bottom of this page.
If you choose to let us do the designs for you, our in-house experts will ensure that the oligonucleotides have optimal LNA™-content and positioning, resulting in efficient target recognition and minimal self-annealing.
Let Exiqon design your knockdown oligonucleotides We are happy to design LNA™ antisense oligonucleotides targeting customer-defined RNA targets. Simply send us the sequence of your target. Antisense inhibitors are available for both in vitro and in vivo applications.
For more information and for ordering, please contact us.
Design your own knockdown oligonucleotides Use the guidelines below to design your own knockdown oligonucleotides. When you are ready to order, just click the "Order this product" button at the bottom of this page.
Oligonucleotide design
- Avoid stretches of 3 or more Gs or Cs.
- Avoid stretches of more than 4 LNA™ bases, except when very short (9-10 nt) oligonucleotides are designed.
- Avoid LNA™ self-complementarity. LNA™ hybridizes very tightly to other LNA™ residues. Check your design using these tools.
- Keep the GC-content between 30-60 %.
- A T m of approximately 75 °C is recommended. Calculate T m using these tools.
- No LNA™ bases should be placed in palindromes (G-C base pairs are more critical than A-T base pairs).
- For in vivo knockdown oligonucleotides, consider using complete phosphorothioate backbones. Also, consider designing cholesterol conjugated oligos for better uptake in the cells.
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LNA™ knockdown oligonucleotides can be used for a number of applications.
In recent studies, Mayer and co-workers used LNA™ oligonucleotides to inhibit pRNA 1, 2 . This RNA binds to a subunit of the chromatin remodeling complex NoRC, which is associated with the silencing of ribosomal RNA genes (rDNA). Upon antisense depletion of pRNA, NoRC was displaced from the nucleoli, rDNA methylation decreased and RNA polymerase I was activated, indicating that pRNA is required for rDNA silencing (Figure 1).
LNA™ antisense oligonucleotides has also been used in vitro to inhibit the RNA component of telomerase. Upon transfecting cells with a 13-mer LNA™ oligonucleotide, the activity of the enzyme was decreased by over 80 % 3 .
In the first in vivo experiment using LNA™ antisense oligonucleotides, Wahlestedt and co-workers injected LNA™/DNA oligonucleotides targeting delta opioid receptor mRNA into rat brains 4 .
Elevated expression of the alpha subunit of Hypoxia-inducible factor-1 (HIF1-α) is associated with poor prognosis in many types of cancer. Greenberger et al. used LNA™ antisense oligonucleotides to inhibit HIF1-α mRNA in vitro and in vivo . Tumor reduction was seen in nude mice implanted with DU145 cells treated with the inhibitor 5 .
Since LNA™ monomers are tolerated by the RNAi machinery, LNA™ can also be incorporated into siRNA. Elmén and co-workers compared LNA™-containing siRNA to traditional siRNA and found that serum half-life was increased and sequence-related off-target effects were reduced when using LNA™-containing siRNA 6 .
1. Mayer et al. Mol. Cell 2006, 22: 351–61.
2. Mayer et al. EMBO Rep. 2008, 9: 774-80.
3. Elayadi et al. Biochemistry 2002, 41: 9973-81.
4. Wahlestedt et al. Proc. Natl. Acad. Sci. USA 2000, 97: 5633-8.
5. Greenberger et al. Mol. Cancer Ther. 2008, 7: 3598-608.
6. Elmén et al. Nucleic Acids Res. 2005, 33: 439-47.
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Figure 1 Effects of LNA™-mediated depletion of pRNA. (Click to learn more)
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