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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.
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.
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.
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.