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Exosomes as Early Indicators of Disease – Small Needles in Large Haystacks?

There has been a lot of chatter about using blood exosomes as a means of early detection of disease. In theory, you isolate the exosomes from a blood sample, and then analyze them in order to detect disease markers. Sounds simple enough, but you really need to know which tissues the exosomes came from. Current dogma states that all cells release exosomes, so then this would mean that it would be very daunting to determine the point of origin of the exosomes in your sample. How many exosomes are there in a few milliliters of blood? I would bet dollars to navy beans that there are billions, which would make it seem almost impossible to detect your relatively low number of diagnostically relevant exosomes from the high background.

Now, cue the Mission-Impossible theme. Researchers at Uppsala University and Vesicode AB have developed a method to quantitate the presence of specific combinations of exosomal surface proteins. These exosomal proteins and combinations can then be used to determine the tissues of origin, and then compared to what is expected from healthy versus diseased tissues.

Specifically, they developed a method that uses antibody-DNA conjugates together with large, single stranded DNA clusters with hundreds of copies of a unique DNA barcode each. Proteins on the surfaces of individual exosomes are tagged with the antibody-DNA conjugates and are then captured in microtiter wells. These individual complexes are then brought together with the DNA clusters, resulting in the incorporation of the barcodes after DNA polymerization. Following PCR and sequencing, the sequences can be sorted; from the data generated, individual exosomes can be identified and matched with surface protein data.

Approaches such as this gives one hope that diseases can be diagnosed and treated much earlier than current methods are able to do. I look forward to the day when my next physical checkup involves only a simple blood sample instead of those more invasive techniques that are dreaded by so many!


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