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Evaluation of 2'-modified oligonucleotides containing 2'-deoxy gaps as antisense inhibitors of gene expression.
The use of a previously described 17-mer phosphorothioate for structure-function analysis of 2'-sugar modifications and the results demonstrate the importance of target affinity in the action of antisense oligonucleotides and of RNase H as a mechanism by which these compounds exert their effects.
Modulation of the Helicase Activity of eIF4A by eIF4B, eIF4H, and eIF4F*
- G. Rogers, N. J. Richter, W. Lima, W. Merrick
- Biology, PhysicsThe Journal of Biological Chemistry
- 17 August 2001
Results indicate that a linear relationship exists between the initial rate or amplitude of unwinding and duplex stability for all factor combinations tested and a simple model of how eIF4B or eif4H affects the duplex unwinding mechanism of eIF 4A is proposed.
Targeted delivery of antisense oligonucleotides to hepatocytes using triantennary N-acetyl galactosamine improves potency 10-fold in mice
Triantennary N-acetyl galactosamine (GalNAc, GN3), a high-affinity ligand for the hepatocyte-specific asialoglycoprotein receptor (ASGPR), enhances the potency of second-generation gapmer antisense…
Further Characterization of the Helicase Activity of eIF4A
It is suggested that eIF4A may interact directly with double-stranded RNA, and recognition of helicase substrates occurs via chemical and/or structural features of the duplex.
Single-Stranded siRNAs Activate RNAi in Animals
Determination of the Role of the Human RNase H1 in the Pharmacology of DNA-like Antisense Drugs*
- Hongjiang Wu, W. Lima, Hong Zhang, Amy Fan, Hong Sun, S. Crooke
- Biology, ChemistryJournal of Biological Chemistry
- 23 April 2004
It is demonstrated that in human cells RNase H1 is responsible for most of the activity of DNA-like antisense drugs, and it is shown that there are several additional previously undescribed RNases H inhuman cells that may participate in the effects ofDNA- like antisense oligonucleotides.
Single-Stranded RNAs Use RNAi to Potently and Allele-Selectively Inhibit Mutant Huntingtin Expression
Competition for RISC binding predicts in vitro potency of siRNA
It is shown that modified siRNAs use the RISC mechanism and lead to cleavage of target mRNA at the same position as unmodified siRNA, indicating that the amount of a cellular component, perhaps RISC, limits siRNA activity.
Structural Analysis of Human Argonaute-2 Bound to a Modified siRNA Guide.
- N. Schirle, Garth A. Kinberger, Heather F Murray, W. Lima, T. P. Prakash, I. MacRae
- Biology, ChemistryJournal of the American Chemical Society
- 12 July 2016
The crystal structure of human Ago2 bound to a metabolically stable siRNA containing extensive backbone modifications is presented and structure-activity analysis reveals that even major conformational perturbations in the 3' half of the siRNA seed region have a relatively modest effect on knockdown potency.
Properties of Cloned and Expressed Human RNase H1*
Cloned His-tag human RNase H1 exhibited a bell-shaped response to divalent cations and pH and displays a strong positional preference for cleavage, i.e. it cleaves between 8 and 12 nucleotides from the 5′-RNA-3′-DNA terminus of the duplex.