A Short Phosphodiester Window Is Sufficient to Direct RNase H-Dependent RNA Cleavage by Antisense Peptide Nucleic Acid
Antisense and Nucleic Acid Drug Development2000Vol. 10(6), pp. 463–468
Citations Over TimeTop 22% of 2000 papers
CHARLOTTE MALCHÉRE, Jeroen C. Verheijen, SANDER VAN DER LAAN, Lionel Bastide, JACQUES VAN BOOM, Bernard Lebleu, IAN ROBBINS
Abstract
The potential pharmacologic benefits of using peptide nucleic acid (PNA) as an antisense agent are tempered by its incapacity to activate RNase H. The mixed backbone oligonucleotide (ON) (or gapmer) approach, in which a short internal window of RNAse H-competent residues is embedded within an RNase H-incompetent ON has not been applied previously to PNA because PNA and DNA hybridize to RNA with very different helical structures, creating structural perturbations at the two PNA-DNA junctions. It is demonstrated here for the first time that a short internal phosphodiester window within a PNA is sufficient to evoke the RNase H-dependent cleavage of a targeted RNA and to abrogate translation elongation in a well-characterized in vitro assay.
Related Papers
- → RNase R mutants elucidate the catalysis of structured RNA: RNA-binding domains select the RNAs targeted for degradation(2009)58 cited
- → Phylogenetic analysis of the structure of RNase MRP RNA in yeasts(2002)45 cited
- → Crystal structure of metagenome-derived LC11-RNase H1 in complex with RNA/DNA hybrid(2013)7 cited
- → Identification of the gene encoding a type 1 RNase H with an N‐terminal double‐stranded RNA binding domain from a psychrotrophic bacterium(2007)9 cited
- → RNase MRP and RNase P share a common substrate(1993)31 cited