Functional nucleic acid-based diagnostics and therapeutics targeting viral genomic RNA must be able to overcome extensive RNA secondary and tertiary structures in order to be effective. This paper demonstrates a new method to improve the accessibility of RNA-cleaving DNAzymes (10-23) to relatively inaccessible target sites within large, structured RNA molecules from SARS-CoV-2, using antisense DNA oligonucleotides (ASOs) that flank the DNAzyme target site.
We show that this method can be used to improve the accessibility and activity of 10-23 to previously inaccessible target sites by as much as 2000-fold. We also use an ASO screening approach to demonstrate that structured regions within large RNA molecules typically exist near the target site, rather than more distal regions.
Overall this method is a cheap, fast and effective way to improve DNAzyme accessibility to inaccessible target sites within any large RNA molecule.
Check out the full paper HERE.