Towards DNA Nanomachines for Cancer Treatment: Achieving Selective and Efficient Cleavage of Folded RNA

Despite decades of efforts, gene therapy (GT) has failed delivering a clinically significant anti‐cancer treatment due, in part, to low selectivity, efficiency and poor accessibility of folded RNA targets. Here, we propose to solve these common problems of GT agents using DNA nanotechnology approach. We designed a deoxyribozyme‐based DNA machine that can (i) recognize a sequence of a cancer biomarker with high selectivity, (ii) tightly bind structured fragment of a housekeeping gene mRNA, and (iii) cleave it with efficiency greater than that of a traditional DZ‐based cleaving agent. The deoxyribozyme DNA machine can potentially become a prototype platform for a new type of anti‐cancer GT agents.

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