Tiny disease trackers could allow doctors to diagnose and treat diseases more effectively

Extracellular vesicles, small packages of cellular material that break off from cells, contain natural tracking numbers, much like you'd find on an Amazon package, that link them to their source.

Kenneth Witwer, a Johns Hopkins associate professor of molecular and comparative pathobiology and neurology, is studying how these particles could allow doctors to diagnose diseases earlier and deliver treatments effectively and easily, without requiring extensive and invasive blood tests.

An RNA vault

Extracellular vesicles are small clumps that bud off from a cell, but unlike a cell, they can't replicate. It's a constant, normal, and natural process that happens in both healthy and diseased cells. As the vesicle is pinched off, some of the interior components of the original cell go along with it. This material, which includes key RNA information, is protected from breaking down because the extracellular vesicle envelops itself with part of the cell's membrane.

Treatment Potential

Interest in using RNA as a biomarker—a biological indicator of disease—isn't new, says Witwer, who has studied extracellular vesicles for more than 15 years. But using RNA found in these cell fragments to map out where cells came from could be revolutionary.

"Extracellular vesicles bear a signature of their origin cell," Witwer says. "The original cell imbues the extracellular vesicle with proteins and other molecules that are characteristic of that original cell. This means we can ideally trace extracellular vesicles back to a specific cancer cell, or maybe a neuron in the brain of an Alzheimer's patient."

Witwer is leading an international team funded by the National Institutes of Health's National Cancer Institute to study how existing imaging and detection technologies, such as cytometry and single cell sequencing, as well as emerging imaging and detection technologies, can be used to understand where a particular extracellular vesicle came from and where it's going. By tracing it back to the source, doctors can best determine how and where to target treatment.

Using this method over other biomarkers provides researchers with a key advantage because the vesicles are relatively abundant and their RNA can be easily amplified. But until recently, single cell sequencing couldn't dive deep enough to examine the extracellular vesicle RNA level, which is a fraction of the size of a cell. A core component of this new NIH project will seek to develop and refine technology for finding and analyzing these tiny packages.

A New Push Forward

Witwer has been working with the NIH since 2016, when he began advising the Extracellular RNA Communication Consortium that was launched in 2013. Several successful years later, the consortium has collected a huge amount of data and published research that is leading to commercial biomarker tests that use extracellular vesicles and RNA to make diagnoses. Now, Witwer's international team, funded by a two-year, $940,000 grant, seeks to improve the methods and devices required for better diagnosis and treatment.

"We now have the opportunity here to introduce new diagnostic tools that are going to do what the medical community has been hoping for, for over a decade," Witwer says. "We'll be able to take someone's blood, saliva, or urine and understand so much more than ever before."

Witwer says he hopes this research will accelerate personalized medicine and personalized approaches to disease, because individuals can respond to the same disease in dramatically different ways. "Extracellular vesicles and the genetic material that they contain will be key to bringing personalized medicine to where we want it to go," he says.