Advantages and disadvantages of LNA
Provided lineup (excerpt) The catalog includes the main LNA amidites: LNA-A(Bz) amidite (CAS: 206055-79-0) LNA-G(dmf) amidite (CAS: 709641-79-2) LNA-T amidite (CAS: 206055-75-6) LNA-C(Bz) amidite (CAS: 206055-82-5) Characteristics of LNA phosphoramidites The most notable feature of LNA is that the 2'-O and 4'-C of the ribose ring are linked (locked) by a methylene bridge. The advantages brought by this structure are remarkable. 1. Advantages of LNA ■ Improved thermal stability (increased T_m value) ■ Enhanced nuclease resistance ■ Excellent mismatch discrimination ability 2. Disadvantages to be aware of and "smart" usage ■ Off-target effects and toxicity risks ■ Lack of flexibility
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Disadvantages and "Smart" Usage You Should Know LNA is not a magic wand that simply works by being introduced. There are points of caution due to its characteristics. ● Risks of Off-Target Effects and Toxicity - Issue: Due to its high affinity, it may bind to unintended mismatched sequences (off-target effects). Additionally, the extensive use of LNA with specific sequence patterns has been reported to potentially cause hepatotoxicity. - Countermeasure: Instead of making the entire sequence LNA, it is recommended to design it as a "Mixmer" mixed with DNA or a "Gapmer" with DNA placed in the center. ● Lack of Flexibility - Issue: The structure is fixed in the C3'-endo conformation, resulting in a loss of flexibility in the double strand. - Countermeasure: If enzyme reactions (such as degradation by RNase H) are expected, careful design of the placement of LNA is necessary.
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