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Modular cell-internalizing aptamer nanostructure enables targeted delivery of large functional RNAs in cancer cell lines
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Modular cell-internalizing aptamer nanostructure enables targeted delivery of large functional RNAs in cancer cell lines
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Journal Article
Modular cell-internalizing aptamer nanostructure enables targeted delivery of large functional RNAs in cancer cell lines
2018
Overview
Large RNAs and ribonucleoprotein complexes have powerful therapeutic potential, but effective cell-targeted delivery tools are limited. Aptamers that internalize into target cells can deliver siRNAs (<15 kDa, 19–21 nt/strand). We demonstrate a modular nanostructure for cellular delivery of large, functional RNA payloads (50–80 kDa, 175–250 nt) by aptamers that recognize multiple human B cell cancer lines and transferrin receptor-expressing cells. Fluorogenic RNA reporter payloads enable accelerated testing of platform designs and rapid evaluation of assembly and internalization. Modularity is demonstrated by swapping in different targeting and payload aptamers. Both modules internalize into leukemic B cell lines and remained colocalized within endosomes. Fluorescence from internalized RNA persists for ≥2 h, suggesting a sizable window for aptamer payloads to exert influence upon targeted cells. This demonstration of aptamer-mediated, cell-internalizing delivery of large RNAs with retention of functional structure raises the possibility of manipulating endosomes and cells by delivering large aptamers and regulatory RNAs.
Large RNAs and ribonucleoprotein complexes have shown potential as novel therapeutic agents, but their targeted delivery to cells is still challenging. Here the authors present a modular aptamer nanostructure for intracellular delivery of RNAs up to 250 nucleotides to cancer cells.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/19
/ 14/34
/ 38/71
/ 82/29
/ Animals
/ Aptamers
/ Aptamers, Nucleotide - administration & dosage
/ Aptamers, Nucleotide - chemistry
/ Aptamers, Nucleotide - genetics
/ Cancer
/ Dogs
/ Fluorescent Dyes - chemistry
/ Humanities and Social Sciences
/ Humans
/ Leukemia
/ Leukemia, B-Cell - metabolism
/ Nanostructures - administration & dosage
/ Payloads
/ RNA
/ Science
/ siRNA
