Evaluating TNA stability under simulated physiological conditions

Chemically modified oligonucleotides are routinely used as diagnostic and therapeutic agents due to their enhanced biological stability relative to natural DNA and RNA. Here, we examine the biological stability of alpha-L-threofuranosyl nucleic acid (TNA), an artificial genetic polymer composed of repeating units of alpha-L-threofuranosyl sugars linked by 2',3'-phosphodiester bonds. We show that TNA remains undigested after 7 days of incubation in the presence of either 50% human serum or human liver microsomes and is stable against snake venom phosphordiesterase (a highly active 3' exonuclease). We further show that TNA will protect internal DNA residues from nuclease digestion and shield complementary RNA strands from RNA degrading enzymes. Together, these results demonstrate that TNA is an RNA analogue with high biological stability. (C) 2016 Elsevier Ltd. All rights reserved.