Selectivity and predictability of Watson-Crick base pairing makes DNA a molecule of choice for the development of DNA-based diagnostic and therapeutic methods. DNA-based computation circuits are capable of analyzing complex sets of biological inputs, where by directly interacting with input molecules, a specific output is produced. This project aims to design first of its kind DNA nanorobot, capable of recognizing RNA inputs generated by cancer cells, and produce RNA cleaving function as an output. The device is designed to recognize sequence of KRAS mRNA with G/A nucleotide substitution in codon 12, a mutation that occurs in 90 % of pancreatic cancer cases. The sensing function is carried out by two deoxyribozymes Dz-1 and Dz-2, which hybridize to the complimentary sequence on the target (Figure 1). As a result, short 21-nucleotide fragment of KRAS RNA is produced. This fragment serves as an activator for the actuating ( RNA cleavage) portion of the nanorobot, that is carried out by a split deoxyribozyme (labeled BiDz-a and BiDz-b ). In the split state, deoxyribozyme is inactive, and cannot catalyze RNA cleavage. To restore RNA cleaving activity, two halves of deoxyribozyme need to be brought together. When activated, split deoxyribozyme binds mRNA for a housekeeping gene, and cleaves it, resulting in the death of the cancer cell. In the preliminary experiments, the RNA cleaving portion of the nanorobot was first designed to bind and cleave the fluorescent substrate.

Developing of a DNA nanorobot with RNA sensing and cleaving functions

2019 Spring National Meeting

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