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Tetrahedral DNA Nanostructure-Delivered DNAzyme for Gene Silencing to Suppress Cell Growth

Meng, Lingxian, Ma, Wenjuan, Lin, Shiyu, Shi, Sirong, Li, Yanjing, Lin, Yunfeng
ACS applied materials & interfaces 2019 v.11 no.7 pp. 6850-6857
cell growth, cell proliferation, drug delivery systems, gene silencing, messenger RNA, nanomaterials, oligonucleotides, single-stranded DNA
DNAzymes are synthetic oligonucleotides that are capable of cleavaging target mRNA to exert gene-silencing activity and are considered as promising therapeutic agents. Dz13 is a DNAzyme that cleaves the mRNA of c-Jun and suppresses the growth of squamous cell carcinomas. However, DNAzymes exhibit low cellular uptake efficacy and require a suitable drug delivery system. In this study, we directly added the Dz13 sequence to the 5′-end of single-stranded DNA to form modified tetrahedral DNA nanostructures (TDN–Dz13). The TDNs were used to deliver the single-stranded DNAzyme Dz13 into cells. Dz13 delivered by the TDNs showed high cellular uptake efficiency and still maintained intracellular gene-silencing activity to cleave the target c-Jun mRNA, which reduced cell proliferation. This study may help find a convenient approach for the delivery of DNAzymes to regulate target genes.