title: Evaluating TNA stability under simulated physiological conditions.
abstract: 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 α-l-threofuranosyl nucleic acid (TNA), an artificial genetic polymer composed of repeating units of α-l-threofuranosyl sugars linked by 2',3'-phosphodiester bonds. We show that TNA remains undigested after 7days 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.
authors.affiliation: Biodesign Institute, Arizona State University, Tempe, AZ 85287-5301, USA.
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Culbertson
authors.affiliation: Biodesign Institute, Arizona State University, Tempe, AZ 85287-5301, USA.
authors.forename: Kartik W
authors.initials: KW
authors.lastname: Temburnikar
authors.affiliation: Biodesign Institute, Arizona State University, Tempe, AZ 85287-5301, USA; Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697-3958, USA.
authors.forename: Sujay P
authors.initials: SP
authors.lastname: Sau
authors.affiliation: Biodesign Institute, Arizona State University, Tempe, AZ 85287-5301, USA; Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697-3958, USA.
authors.forename: Jen-Yu
authors.initials: JY
authors.lastname: Liao
authors.affiliation: Biodesign Institute, Arizona State University, Tempe, AZ 85287-5301, USA; Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697-3958, USA.
authors.forename: Saikat
authors.initials: S
authors.lastname: Bala
authors.affiliation: Biodesign Institute, Arizona State University, Tempe, AZ 85287-5301, USA; Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287-5301, USA; Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697-3958, USA. Electronic address: jchaput@uci.edu.
authors.forename: John C
authors.initials: JC
authors.lastname: Chaput
mesh_terms: D001088:Arabinonucleotides / Q000493:pharmacokinetics; D004355:Drug Stability; D006207:Half-Life; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008862:Microsomes, Liver / Q000187:drug effects; D009841:Oligonucleotides / Q000737:chemistry* / Q000493:pharmacokinetics; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000378:metabolism; D012266:Ribose / Q000737:chemistry; D013780:Tetroses / Q000737:chemistry*
chemical_list: C507672:2'-deoxy-2'-fluoro-beta-D-arabinonucleic acid; D001088:Arabinonucleotides; D009841:Oligonucleotides; D013780:Tetroses; D012266:Ribose; D010727:Phosphoric Diester Hydrolases; C073321:erythrose
keywords: Biological stability; RNA analogue; Threose nucleic acid