Progress and Application Potential of Exosomes

Posted by Ilsa Miller on December 2nd, 2020

As a member of the central dogma, RNA plays a crucial role in the transmission of genetic information. Even in the 1970s and 1980s, researchers have found that RNA not only hides in cells, they can be coated by extracellular vesicles to flow between tissues and organs through the blood circulation, and this special structure is called exosomes. But this small finding has not attracted enough attention. After more than 30 years of silence, extracellular RNA, also known as exRNA, a type of exosome, seems to usher in dawn. The researchers began to explore why cells excrete RNA and how it is excreted, and whether exRNA can play a role in the detection and treatment of diseases.

In-depth mechanistic studies bring explosive application prospects, and exploration around exosomes has continued. From an erroneous experiment, Tosar found that intact ribosomes may exist extracellularly. Past studies have shown that exRNA is protected by extracellular vesicles, but there is increasing evidence that long fragments of exRNA without vesicle encapsulation are also present, suggesting that exRNA may bind to ribosomes and be protected by ribosomes. Tosar's study is a major breakthrough, confirming scientists' long-standing speculation. Tosar also proposes a bold model in which translation events are likely to also exist in the extracellular matrix, that is to say that ribosomes are likely to be active and proteins are not only made inside the cell, and if so, this result may subvert past perceptions.

It is generally accepted that release of exRNAs is a way of cell-to-cell communication. By intercepting these exRNA-containing exosomes, we are roughly able to discern early signals of the disease. Before the onset of disease symptoms, the exRNA level in the plasma of the affected population will be different from the exRNA level of the normal population, and by finding the difference, it can be used as a criterion for prediction before the onset of symptoms.

For example: zhong sheng's group from the University of California studied numerous clinical samples using the latest SLIVER-seq technology to determine that changes in the amount of PHGDH in plasma can be used as a marker before the onset of Alzheimer's disease.

The use of exRNA for the prediction of disease is problematic and very sensitive, but this method is also very troublesome. The exosomes encapsulating exRNA have different sizes, and exosomes may also overlap with other metabolites. How do we distinguish between exosomes from diseased tissue and those from healthy tissue, how to carry out the next step after obtaining exosomes, and how to reduce the noise of PCR. Many laboratories have been designing various devices to solve these problems. Combined with microfluidic means, we have been able to purify exosomes at high speed and yield and accurately label and capture them.

Exosome delivery of exRNA has also provided inspiration to scientists in the field of drug delivery. There is immune rejection in the delivery of drugs through both artificial lipid membranes and nanoparticles, while there is no such concern in engineering naturally occurring exosomes in vivo to achieve drug delivery. Some laboratories have even demonstrated that exosomes have a higher affinity for their tissues of the same origin, and this conclusion helps us to achieve directional transport of drugs.