An RNA-cleaving threose nucleic acid enzyme capable of single point mutation discrimination

Cellular uptake, tissue penetration, biodistribution, and biosafety of threose nucleic acids: Assessing in vitro and in vivo delivery

“…TNA possesses attractive properties of chemical simplicity, high binding specificity towards DNA/RNA, tertiary structure folding capability, and excellent biological stability, holding great potential in biology study and biomedical applications [ 21 , 22 , 29 ]. So far, TNA has been widely used in various biomedical applications such as aptamer selection [ 22 , 29 ], XNAzyme discovery [ [29] , [30] , [31] , [32] , [33] ], gene regulation [ 25 , 26 , 28 ], and immunotherapy [ 24 , 27 ]. In this work, we systematically investigated the interactions of TNA oligonucleotides with living organisms, including cellular uptake, penetration in 3D cell culture, pharmacokinetics, tissue biodistribution, and in vivo biosafety for the first time.…”

“…We believe that the TNA accumulation in the kidneys was possibly due to the preferential uptake by the kidney proximal tubule cells [ 40 , 62 ]. TNA oligonucleotides for gene regulation have been reported in the past few years [ [25] , [26] , [27] , [28] , [30] , [31] , [32] ]. For example, Chaput and coworkers demonstrated the TNA CPG strands can activate innate immune responses with induction of relevant mRNAs and B-cell activation [ 27 ].…”

“…Very recently, Yu et al. reported the in vitro isolation of TNA-based enzymes with RNA-cleaving activity [ 30 ]. One selected TNA enzyme, Tz1, can specifically cleave the mutant epidermal growth factor receptor (EGFR) RNA substrate with a single point mutation.…”

“…The developed linear gene exhibited enhanced enzymatic resistance and serum stability and elicited a potent and persistent EGFP gene expression in eukaryotic cells [ 28 ]. Most recently, Yu and coworkers reported TNA-based enzymes with RNA-ligation or RNA-cleavage activities [ 29 , 30 ]. Chaput and coworkers also demonstrated that the introduction of TNA and 2′-fluoroarabino nucleic acid (FANA) modifications into a classic DNAzyme 10–23 (X10-23) significantly enhanced the biological stability and catalytic activity.…”

From polymerase engineering to semi-synthetic life: artificial expansion of the central dogma

“…They also reported the introduction of XNA modifications, including FANA and TNA nucleotides, into an existing DNAzyme scaffold for the construction of a novel enzyme, X10-23, with enhanced biological stability and good catalytic activity, and demonstrated the application of X10-23 in gene knockdown and pathogen detection [207][208][209] . Recently, selection of TNA enzymes with RNA cleavage or ligation activity has been reported by Yu and co-workers 210,211 .…”