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| Open AccessImaging small molecule-induced endosomal escape of siRNA
Therapeutic siRNA becomes trapped in endosomes, limiting its efficacy. Here the authors use fluorescently-tagged galectin-9 as a biosensor for membrane damage to monitor endosomal escape of cholesterol-conjugated siRNA following treatment of small molecule membrane-destabilising drugs.
- Hampus Du Rietz
- , Hampus Hedlund
- & Anders Wittrup
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Article
| Open AccessNaturally-occurring cholesterol analogues in lipid nanoparticles induce polymorphic shape and enhance intracellular delivery of mRNA
Endosomal sequestration of lipid-based nanoparticles is a barrier to delivery of nucleic acids. Here the authors test an array of cholesterol variants and perform in-depth investigation of nanoparticle shape, internal structure and intracellular trafficking.
- Siddharth Patel
- , N. Ashwanikumar
- & Gaurav Sahay
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Article
| Open AccessIn vivo rendezvous of small nucleic acid drugs with charge-matched block catiomers to target cancers
Nanoparticle delivery of siRNA has problems with penetration and off target accumulation. Here, the authors report on the development of Y-shaped block catiomers which dynamically wrap around siRNA; demonstrate increased circulation times and delivery into hard to reach brain and pancreas tumour models.
- Sumiyo Watanabe
- , Kotaro Hayashi
- & Kazunori Kataoka
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Article
| Open AccessModular cell-internalizing aptamer nanostructure enables targeted delivery of large functional RNAs in cancer cell lines
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.
- David Porciani
- , Leah N. Cardwell
- & Donald H. Burke
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Article
| Open AccessA DNA dual lock-and-key strategy for cell-subtype-specific siRNA delivery
Delivery of siRNA to target cells is essential for in vivogene therapy. Here the authors demonstrate an oligonucleotide aptamer that targets therapeutic siRNA to a specific cell type.
- Kewei Ren
- , Ying Liu
- & Huangxian Ju