Cut and Paste for Cancer Treatment: A DNA Nanodevice that Cuts Out an RNA Marker Sequence to Activate a Therapeutic Function

Angew Chem Int Ed Engl. 2020 Nov 16;59(47):21190-21194. doi: 10.1002/anie.202006384. Epub 2020 Sep 7.

Abstract

DNA nanotechnology uses oligonucleotide strands to assemble molecular structures capable of performing useful operations. Here, we assembled a multifunctional prototype DNA nanodevice, DOCTR, that recognizes a single nucleotide mutation in a cancer marker RNA. The nanodevice then cuts out a signature sequence and uses it as an activator for a "therapeutic" function, namely, the cleavage of another RNA sequence. The proposed design is a prototype for a gene therapy DNA machine that cleaves a housekeeping gene only in the presence of a cancer-causing point mutation and suppresses cancer cells exclusively with minimal side effects to normal cells.

Keywords: DNA nanotechnology; KRAS gene; deoxyribozymes; gene therapy; split probes.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Base Sequence
  • Biomarkers, Tumor / genetics*
  • DNA / chemistry*
  • Genetic Therapy*
  • Humans
  • Mutation
  • Nanotechnology*
  • Neoplasms / genetics*
  • RNA, Neoplasm / genetics*

Substances

  • Biomarkers, Tumor
  • RNA, Neoplasm
  • DNA