Authors
Zhou, Z., Zhang, L., Wang, X., Zhang, C., Yan, Q., Wang, S., Liu, H., Su, X.
Abstract
Extracellular microRNAs (miRNAs) contribute to metastasis through communication between tumour cells and their microenvironment, yet their sustained, sequence-selective depletion remains challenging. Here we report Programmable RNA-Intercepting Molecular Eraser (PRIME), a membrane-anchored DNA nanomachine that organizes miRNA recognition and catalytic degradation at the cell surface. A double-tetrahedral DNA scaffold positions a programmable recognition hairpin beside RNase H. Target binding generates an RNA/DNA hybrid for RNase H-mediated cleavage, and product release resets the hairpin for subsequent degradation cycles. Membrane-anchored PRIME depleted matched extracellular miRNAs by 70.6-89.4% across lung, breast and cervical cancer cell models. Multi-target PRIME (M-PRIME) inhibited migration by 71.3-96.0% in Transwell assays across these models. To evaluate its therapeutic potential, we established an orthotopic lung-tumour model and an early-intervention breast-cancer lung-colonization model in mice. Aptamer-directed M-PRIME combined with gemcitabine reduced pulmonary tumour burden by 74.5% in established lung tumours and 93.2% in the lung-colonization model. These effects were consistent with PRIME-mediated extracellular miRNA degradation, with circulating target miRNA levels reduced by 77.5-98.7% relative to gemcitabine alone. Together, these findings establish a programmable material strategy for sustained extracellular RNA depletion and support its potential to enhance chemotherapy in preclinical tumour models.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 02 Oct 2026.
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