Abstract: An improved threose nucleic acid (TNA) polymerase exhibits both increased efficiency and increased capability relative to earlier TNA polymerases, with a catalytic rate of ~1 nt/s and >99% fidelity. The new enzyme shows reduced activity against dNTPs, maintains ultrahigh thermal stability, and readily accepts C5-modified TNA nucleoside triphosphates (tNTPs). Also provided are methods for making and using the improved TNA polymerase. The TNA polymerase.

Abstract: Molecules, materials, and methods for gene silencing utilize a modified 10-23 DNAzyme that functions with unparalleled catalytic activity under physiological conditions. The enzyme was discovered through iterative cycles of design that were guided by structural information available on the folding topology and metal-ion binding sites of Dz 10-23. The new enzyme can achieve ~65 turnovers in 30 minutes, a feat only previously witnessed by the unmodified parent sequence under forcing conditions of elevated Mg2+ and pH, making it the fastest known RNA-cleaving DNAzyme under physiological conditions.

Abstract: Efforts to use RNA-cleaving DIMA enzymes (DNAzymes) as gene silencing agents in therapeutic applications have stalled due to their low efficacy in clinical trials. Here the present invention reports a xeno-nucleic acid (XNA) modified version of the classic DNAzyme 10-23 that achieves multiple turnover activity under cellular conditions and resists nuclease digestion. The new reagent overcomes the problem of product inhibition limiting previous 10-23 designs using molecular chemotypes with DNA. FANA, and TNA backbone architectures that balance the effects of enhanced biological stability with RNA hybridization and divalent metal ion coordination. In cultured mammalian cells. X 10-23 facilitates persistent gene silencing by efficiently degrading exogenous and endogenous mRNA transcripts. Together, these results demonstrate that new molecular chemotypes can improve the activity and stability of DNAzymes, and may provide a new route for nucleic acid enzymes to reach the clinic.

Abstract: The present invention provides methods for synthetic antibodies, methods for making synthetic antibodies, methods for identifying ligands, and related methods and reagents.