The recently described in vivo gene silencing activity of a xeno nucleic acid (XNA)-modified version of the classic 10-23 DNAzyme (X10-23) has created substantial interest1-3. Our data suggest that the core claim of the manuscript-that the observed gene silencing activity is mediated by the RNA endonuclease catalytic activity of the X10-23 DNAzyme (rather than an antisense effect)-should be reconsidered. We have arrived at this opinion both through examination of the data in the Nature Chemistry paper (Wang et al.1), a companion paper in the Journal of the American Chemical Society (Nguyen et al.2) and by comparison with results we have obtained with the X10-23 DNAzyme (kindly provided by the authors) targeting an RNA sequence (residues 202-215) from exon 2 of the oncogene KRAS (reported as exon 1 in ref.'). Further supporting data are provided by examination of the activities of other modified versions of the 10-23 DNAzyme, as well as all-FANA XNAzymes4, also targeting RNA sequences in KRAS exon 2.
Alexander I. Taylor、Philipp Holliger
展开 >
Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK
MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK
NSTL
