Mikhail V Dubovichenko, Daria D Nedorezova, Christina Patra, Valeria S Drozd, Vladimir S Andrianov, Anna I Ashmarova, Vivian O Nnanyereugo, Ahmed A Eldeeb, Dmitry M Kolpashchikov
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Marker-Dependent Cleavage of RNA by Binary (split) DNAzyme (BiDz) and Binary DNA Machines (BiDM).
Oligonucleotide gene therapy (OGT) can be used to suppress specific RNA in cells and thus has been explored for gene therapy. Despite extensive effort, there is no clinically significant OGT for treating cancer. Low efficiency of OGT is one of the problems. Earlier, we proposed to address this problem by suppressing the most vital genes in cancer cells e. g. housekeeping genes. To achieve specific activation of the OGT agents in cancer but not in normal cells, we designed a binary (split) DNAzyme (BiDz) activated by cancer-related nucleic acid sequences. This work is devoted to BiDz optimization for efficient cleavage of structured RNA targets upon activation with a cancer marker-related sequence. To achieve efficient binding of folded RNA, the BiDz was equipped with RNA binding/unwinding arms to produce 'Binary DNA-nanomachines' (BiDM). It was demonstrated that BiDM can improve both the rate and selectivity of RNA cleavage in comparison with BiDz. For the best selectivity, single-nucleotide variations should be recognized by the strand detached from the common DNA scaffold of BiDM. Further development of DNA nanotechnology-inspired agents can advance OGT in treating cancer, viral infections, and genetic disorders.
期刊介绍:
ChemBioChem (Impact Factor 2018: 2.641) publishes important breakthroughs across all areas at the interface of chemistry and biology, including the fields of chemical biology, bioorganic chemistry, bioinorganic chemistry, synthetic biology, biocatalysis, bionanotechnology, and biomaterials. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies, and supported by the Asian Chemical Editorial Society (ACES).