Binary Antisense Oligonucleotide Agent for Cancer Marker-Dependent Degradation of Targeted RNA
Valeriia S. Drozd, A.A. Eldeeb, Dmitry M. Kolpashchikov, Daria D. Nedorezova
Abstract
Antisense oligonucleotide technology is one of the most successful gene therapy (GT) approaches. However, low selectivity of antisense agents limits their application as anticancer drugs. To achieve activation of antisense agent selectively in cancer cells, herein, we propose the concept of binary antisense oligonucleotide (biASO) agent. biASO recognizes an RNA sequence of a gene associated with cancer development (marker) and then activates RNase H-dependent cleavage of a targeted messenger RNA. biASO was optimized to produce only the background cleavage of the targeted RNA in the absence of the activator. The approach lays the foundation for the development of highly selective and efficient GT agents.