Reategui and Lee win NIH grant supporting novel approach to extracellular vesicle analysis
The dream of prolonging life by detecting and treating diseases like cancer before the disease has a chance to take hold is one that scientists have been pursuing for years. Now, Assistant Professor and Principal Investigator Eduardo Reátegui and Professor Emeritus and Co-PI L. James Lee are steps closer to realizing this capability, aided by an $821,000 first-phase grant from the Common Fund of the National Institutes for Health. The funded proposal is entitled "Microfluidics Array-Based Sorting, Isolation, and RNA Analysis in Single Extracellular Vesicles."
The grant will support the study of extracellular vesicles (EVs)--different types of nanometer-sized particles naturally secreted by both healthy and cancerous cells that are present in biofluids such as blood, urine, and cerebral spinal fluid. EVs contain various biomolecules including DNAs, RNAs, proteins, and metabolites and play a pivotal role in cell-to-cell communication, acting as important mediators of intercellular communication that influence both physiological and pathological conditions.
EVs have attracted considerable interest in the scientific community, but current methods of isolating and characterizing EVs are technically challenging. Traditionally, the molecular content of EVs is analyzed in bulk, which only provides an average of the overall RNA/DNA and protein content while resulting in the loss of molecular information of individual EVs. Therefore, there is a critical need to develop technologies that provide an accurate and efficient analysis of molecular content within individual EVs.
Reátegui and Lee are particularly interested in characterizing EVs from biofluids from cancer patients and have proposed an integrated system to analyze EVs and their RNA cargo in situ at the single vesicle level. The method involves first sorting the EVs from biofluids into well-defined size-based subpopulations and then capturing them by surface expression. After distributing each EV subpopulation, they will analyze their RNA content in situ using high-resolution fluorescence microscopy.
"This process attains an unprecedented level of resolution for detecting cancer with just a few EVs," Reátegui said. "It is the highest resolution available, and makes detecting early-stage cancer much more achievable."
The process could have applications not only in EV diagnostics but also in EV therapeutics, which are being increasingly explored since EVs can surmount biological barriers to transfer bioactive components to other cells. Bioengineered EVs could potentially act as delivery vehicles for therapeutic agents for use in tissue regeneration and modulating immunity, or offer an alternative to stem cell therapy by silencing or activating specific genes.
The first phase of the NIH UG3 grant lasts for two years and includes predesignated milestones. Should the researchers reach the two milestones within that time, they will receive an additional $1.2 million for a period of another two years.
The research is a multidisciplinary effort that includes The University of Texas MD Anderson Cancer Center, one of the original three comprehensive cancer centers in the country, and the Institute for Systems Biology in Seattle.