March 15, 2014 (Vol. 34, No. 6)
Enal Razvi Ph.D. Managing Director Select Biosciences
There is growing interest in the concept of extracellular vesicles as carriers of protein and nucleic acid biomarkers. In this context, exosomes are garnering a significant amount of research attention since they are numerous, are found in most biological fluids, contain protein and RNA molecules derived from the cell they are produced from, and can be harvested and analyzed to understand their cargo. Given that exosomes can be harvested from many biological fluids (blood, urine, cerebrospinal fluid, breast milk, etc.), they constitute a means to perform liquid biopsies with minimal invasiveness, less patient discomfort, and cost-effectively.
Given the potential utility of exosomes as circulating biomarkers, technologies are being developed to purify and analyze these vesicles from biological fluids. The gold standard methodology in this space employs ultracentrifugation and density gradients to capture the bona fide exosome population from the morass of vesicles contained within biological fluids.
This procedure involves a complicated workflow, is cumbersome, requires high amounts of starting material, and is not amenable to automation. Therefore, ultracentrifugation-based approaches cannot be candidates for clinical deployment if exosome interrogation ultimately translates from research to clinic. Therefore the market needs to develop high-throughput approaches.
The following represents the classes of exosome-capture methodologies that have been developed to date:
- Precipitation-based approaches
- Capture-based approaches using antibodies on the surface of exosomes to capture exosomes (or sub-populations thereof) immobilized on the surface of magnetic beads
- Capture-based approaches utilizing columns
Figure 1 presents the segmentation of the marketplace based on the types of methodologies deployed for exosome isolation—this pie chart therefore reflects the quantitative breakout of the methodologies utilized currently for exosome isolation. Note from this figure that ultracentrifugation represents currently half the market and other approaches carve up the other half of this space.
As part of our market analysis we sought to also understand the types of downstream applications that are currently performed on the captured exosomes—in this manner providing a picture of the research activities performed downstream by the research community—the data are presented in Figure 2.
Taken together these data illustrate the types of manipulations being performed on exosomes subsequent to their capture/purification and provides insight on the biomarker cargo that is being interrogated.
There currently are three contender classes for circulating biomarkers: Extracellular vesicles, Circulating tumor cells (CTCs), and Circulating DNA. The goal of deploying these biomarker classes is to provide substrates for liquid biopsies. Currently there is interest in evaluating these classes in different diseases. Over the coming years, we’ll see a shakeout vis-à-vis the different biomarker classes and evolution of the market opportunity.
Enal Razvi, Ph.D. (firstname.lastname@example.org), is biotechnology analyst, managing director, Select Biosciences.