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A multifunctional DNA nano-scorpion for highly efficient targeted delivery of mRNA therapeutics.

ABSTRACT: The highly efficient cancer cell targeted delivery plays an important role in precise targeted therapies. Herein, a multifunctional DNA nano-scorpion nanostructure (termed AptDzy-DNS) functioned with aptamers and DNAzyme is developed for highly efficient targeted delivery of mRNA therapeutics in gene therapy. The designed AptDzy-DNS is self-assembled with specific aptamers as "scorpion stingers" for targeting tumor cell and DNAzymes as "scorpion pincers" for targeted gene therapy by cleaving mRNA into fragments. The as-prepared AptDzy-DNS can effectively distinguish cancer cells from normal cells by specific cross-talking between aptamers on AptDzy-DNS and overexpressed cell-surface receptors. In the process of gene therapy, by reacting with Mg²⁺-dependent DNAzyme on AptDzy-DNS, the mRNA oligonucleotide in cancer cell is auto-cleaved into broken strand, failing to be translated into corresponding protein. Following, the downregulation protein can block cancer cell growth and realize highly efficient targeted therapies. The results demonstrate that the multifunctional AptDzy-DNS shows promise for targeted cancer cell discrimination, highly efficient targeted delivery of mRNA therapeutics in gene therapy. Thus, this developed strategy provides impressive improvement on gene targeted therapy and paves the way for application of AptDzy-DNS in human cancer targeted therapies.

SUBMITTER: Li D

PROVIDER: S-EPMC6033943 | biostudies-literature |

REPOSITORIES: biostudies-literature

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