Fast-Track proposals will not be accepted.
Direct to Phase II will not be accepted.
Phase II budget and duration information is provided to assist Phase I offerors with their long-term strategic planning.
Number of anticipated awards: 2 – 3
Budget (total costs, per award): Phase I: up to $300,000 for up to 9 months
Phase II: up to $2,000,000 for up to 2 years
PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED.
Both normal and cancer tissues shed exosomes and other vesicles into body fluids. Tissue-shed exosomes are found in several body fluids including amniotic fluid, breast milk, bronchoalveolar fluid, cerebrospinal fluid, malignant ascites, plasma, saliva and urine. Exosomes collected from the blood and other body fluids of patients diagnosed with various cancers were shown to contain tumor suppressors, phosphoproteins, proteases, growth factors, bioactive lipids, mutant oncoproteins, oncogenic transcripts, microRNA and genomic DNA fragments. Exosomal trafficking and reciprocal exchange of molecular information among different organs and cell types were reported to contribute to cell-to-cell communication, horizontal cellular transformation, cellular reprogramming, functional alterations, regulation of immune response, and metastasis. In functional studies, exosomes shed by tumors, referred to as oncosomes, were reported to activate normal epithelial cells to form tumors, while exosomes from healthy individuals appear to have anti-tumor characteristics. Comparative molecular profiling of normal tissue-derived exosomes and tumor-derived oncosomes in blood and other body fluids may therefore offer a non-invasive or minimally invasive way to assess carcinogenesis; cancer risk; tumor initiation, promotion, development and progression, metastasis in tissues; survival and treatment response, and the knowledge gained may lead to better cancer prevention/care/control. The major bottleneck for using oncosomes in cancer research or clinical care is in obtaining enriched preparations of oncosomes from body fluids. Existing technologies are based on centrifugation, precipitation/centrifugation or affinity purification, which are labor intensive, time consuming, or biased because they are based on known exosomal markers. Furthermore, existing approaches impose significant stresses on these vesicles and potentially compromise their biological integrity and viability for various downstream uses. Therefore, the goal of this proposal is to accelerate the development of technologies for differential isolation and enrichment of tissue-derived exosomes and tumor-derived oncosomes which will be useful for comparative molecular profiling or therapeutic purposes. Given the potential of exosomes and oncosomes for basic research and clinical applications, proposed technology platforms should be capable of processing a large number of samples each with significant volumes and be useful for profiling multiple body fluids from multiple cancer types. Of further interest are technology proposals amenable to low-cost production, appropriate for handling large number of samples, and useful for profiling multiple body fluids from multiple cancer types to conduct molecular analysis studies in population science.
The biospecimen sources for exosomes or oncosomes isolation and enrichment can be blood, plasma, serum, urine, saliva, amniotic fluid, breast milk, bronchoalveolar lavage, cerebrospinal fluid, peritoneal fluid, malignant ascites or other types of body fluids or effusions. In Phase I, the technology development should focus on isolation and enrichment and obtaining distinct preparations of exosomes and oncosomes. In Phase II, the focus should be adopting the technology developed in phase I to isolating and enriching exosomes and oncosomes from multiple body fluids in multiple cancer types.
The goal of this contract proposal is 1) to support the development of large scale (capable of handling a large volume of a body fluid) or high-throughput (capable of isolating and exosomes or oncosomes from large number of samples in a finite time) technologies for differential isolation of tissue-specific exosomes and tumor-derived oncosomes from any body fluid(s), and 2) to obtain enriched, distinct preparations useful for downstream comparative molecular profiling or therapeutic use. Applicants must propose to develop an efficient and cost effective platform for complete isolation and segregation of extracellular vesicle populations, with particular emphasis on yielding pure exosome or oncosome populations that are morphologically and functionally intact. The technology should preferably establish automated workflows and reduce human intervention to obtain enriched distinct preparations of exosomes and oncosomes.
To apply for this topic, offerors should have a proof-of-concept prototype platform with demonstrated capability for isolating exosomes from complex solutions. Preference will be given for proposals with demonstrated capability for further isolating oncosomes from the general exosome population. They should demonstrate sufficient expertise and necessary resources for robustly characterizing captured oncosomes, and verifying persistence of their biological integrity.
Applicants are required to obtain distinct preparations of exosomes and oncosomes, which originated in a specific tissue/tumor, from routinely collected fresh or archived body fluids. They should demonstrate integrity, quantity and reproducibility of isolation and separation using physicochemical and functional studies. This solicitation is not intended for developing technologies for molecular profiling exosomal or oncosomal cargo.