RNA is now known to travel outside cells to tissues around the body. Researchers are working out whether they can exploit this extracellular RNA to detect and treat disease.
Nature Outlook |
RNA is finding a new role in medicine. Once thought to exist only within cells, the molecule is now known to travel all over the body, under the protection of ‘extracellular vesicles’. Scientists are studying the potential of extracellular RNA for detecting and treating disease.
Features and comment
Tests that detect extracellular RNA to spot cancer, heart disease and other conditions are in development.
Philip W. Askenase explains why naturally occurring exosomes are better for drug discovery.
A serendipitous finding led Juan Pablo Tosar to uncover the protein-making machinery outside cells — a discovery that has scientists rethinking fundamental assumptions.
Kenneth Witwer says that RNA in food could have profound effects on the human digestive system and on health more generally.
Studies have suggested that genetic material can be transferred from diet. But some researchers have their doubts.
A decade after microRNAs were found in mother’s milk, scientists are still trying to work out why they are there and how they affect health.
In exosomes, our bodies have an efficient means of transmitting RNA information. Researchers want to use it to deliver drugs.
Vesicles secreted by stem cells might give clinicians a safer and simpler alternative to cell therapy, but researchers are still grappling with how best to prepare and study these tiny particles.
Some studies have suggested that plants and fungi exchange RNA through extracellular vesicles. This has led some scientists to develop crop sprays that contain RNA.
A biomarker for PTSD, RNA to help kidney repair and other highlights from clinical trials and laboratory studies.
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Tissue fixation with formaldehyde and a water-soluble carbodiimide crosslinker (EDC) leads to retention of extracellular vesicles within tissues and allows for reliable extracellular vesicle imaging for semiquantitative imaging applications.
Large quantities of extracellular vesicles produced via cellular nanoporation, and loaded with endogenously transcribed therapeutic mRNAs and targeting peptides, boost therapeutic outcomes in vivo.
The LC3-conjugation machinery specifies the loading of RNA-binding proteins into extracellular vesicles
Leidal et al. show that the LC3-conjugation pathway, which is part of the autophagy machinery, controls extracellular vesicle cargo loading and secretion of RNA-binding proteins.
A CRISPR-Cas9-based reporter system for single-cell detection of extracellular vesicle-mediated functional transfer of RNA
Extracellular vesicles (EV) facilitate intercellular transfer of biological material including RNA, but the regulatory mechanisms for their formation and transfer are incompletely known. Here the authors develop a CRISPR-based reporting system to detect the transfer of guide RNAs and identify genes not previously linked to EV-mediated RNA delivery.
Adult stem cell companies are pivoting their businesses to commercialize exosomes as therapeutics.
Mutant KRAS is a common driver of pancreatic cancer, and decreasing its expression with siRNA is a potential strategy to forestall pancreatic tumour growth. To improve delivery of short interfering RNA to the pancreas, Raghu Kalluri and colleagues harness exosomes and show that these endogenous vesicles can bypass immune clearance better than artificial liposomes, probably owing to expression of CD47 in their membrane. The iExosomes are uptaken preferentially by pancreatic tumour cells. The authors suggest that this uptake is facilitated by increased macropinocytosis. iExosomes are able to reduce KRAS oncogenic signalling and reduce tumour growth in mouse models of pancreatic cancer.
Reduction of the therapeutic dose of silencing RNA by packaging it in extracellular vesicles via a pre-microRNA backbone
Integrating silencing RNA into the backbone of a microRNA that is highly enriched in small extracellular vesicles reduces the therapeutic dose of the silencing RNA.