Locked Nucleic Acids (LNA) Vs. Bridged Nucleic Acids (BNA)

There are numerous chemical modifications commonly used for the synthesis of oligonucleotides for a variety of reasons. For example, to increase the phosphate backbone's stability, adjust duplex stability, change the oligo's conformation, or increase its ability to penetrate a lipid bilayer. Recently scientists commonly incorporate a modified sugar moiety into an oligonucleotide. Changing the sugar moiety generally increases nuclease resistance and binding affinity to a complementary target. Here we focus on three popular DNA analogs:

  LNA  (Locked Nucleic Acids),

  BNA  (Bridged Nucleic Acids), and

  2’-F-RNA.


Locked Nucleic Acids (LNAs) gained their notoriety from incorporation into probes and siRNAs. Probes and oligonucleotides modified with LNAs are available at Bio-Synthesis. However, Bio-Synthesis offers other modified monomers with the same or even better properties than LNA.

One modified monomer that has gained notoriety is 2’-F-RNA. Incorporation of 2’-F-RNA into oligonucleotides increases the Tm of the duplex by about 1 to 2 ^oC per substitution. Like LNA and other sugar-modified bases, oligonucleotides containing 2’-F-RNA are more resistant to degradation in-vitro and in-vivo. LNA received its name due to its ability to lock a nucleotide into the 3’-endo (North) conformation. A-Form duplexes often have his 3'-endo conformation as well. 2’-F-RNA nucleotides also prefer a C3'- endo/north conformation. However, unlike LNA, 2’-F-RNA nucleotides can undergo pseudorotation of the ribose.

Antisense and siRNA oligonucleotides often contain 2'-F-RNA substitutions because they enhance gene silencing and increase the effectiveness of native siRNA. Still, its popularity is due to its lower cost compared to LNA. Bio-Synthesis also offers 2’-F-RNA to suit your research needs.

The incorporation of Bridged Nucleic Acids (BNA) monomers, a third new modification, into oligonucleotides is also possible. Currently, Bio-Synthesis exclusively offers custom oligonucleotides modified with BNA. BNA is closely related to LNA and developed by Takeshi Imanishi in Japan. Oligonucleotides containing 2’,4’-BNA perform as well as and even better than LNA modified oligonucleotides. BNA has a very high target affinity, similar to or even higher than that of LNA. It increases the Tm per modification by 5 to 6 ^oC when binding to complementary RNA. Additionally, BNA shows enhanced triplex formation, improved resistance to nuclease depredation, and more use in antisense and probe applications than LNA or 2’-F RNA.