Antisense oligonucleotides and their mode of action

Successful binding, however, does not depend alone upon Watson-Crick base complementary. It is also influenced by higher-order secondary and tertiary structures adopted by the RNA. 

CH14 NUCLEIC-ACID- AND CELL-BASED THERAPEUTICS 

However, native antisense oligonucleotides also suffer from a number of disadvantages, which are ultimately responsible for numerous disappointing trial results, and the fact that, after almost two decades of clinical investigation, only a single product has gained approval to date. Disadvantages include  

Some progress has been made to overcome such difficulties, and continued progress in the area is expected to render the next generation of oligos more therapeutically effective. 

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