The National Academies Logo
Research Associateship Programs
Fellowships Office
Policy and Global Affairs

Participating Agencies - NIST

  Sign InPrintable View

Opportunity at National Institute of Standards and Technology (NIST)

Analytical Metrology for Isolating, Purifying and Characterizing Extracellular Vesicles (EVs) for Development and Delivery of Gene and Protein-Based Therapeutics

Location

Material Measurement Laboratory, Biosystems and Biomaterials Division

RO# Location
50.64.41.C0414 Gaithersburg, MD

Please note: This Agency only participates in the February and August reviews.

Advisers

Name E-mail Phone
Nelson, Bryant C. bryant.nelson@nist.gov 301.975.2517
Wang, Lili lili.wang@nist.gov 301.975.2447

Description

Extracellular vesicles (EVs), and in particular exosomes, have the potential to revolutionize the development and efficient delivery of gene and protein therapeutics. Due to their natural non-immunogenicity and their inherent capacity to target specific cell types with no or minimal off-target selection, exosomes are currently being investigated as therapeutic agents in multiple disease models (1). The most established method for isolating exosomes from biological samples (biofluids and/or cell cultures) is based on differential centrifugation (preparative ultracentrifugation), although other methods such as magnetic or immunoaffinity separation and size exclusion chromatography are also utilized (2). Robust purification and analytical characterization of the purified exosome fractions is required due to sample heterogeneity (e.g., microvesicles mixed with exosomes) and sample contamination by exomeres, protein aggregates, microsomes, etc., before the isolated exosomes can continue down the development pipeline toward the therapeutic stage. In addition, it is important to be able to discriminate between the different sub-classes (membrane compositions) of purified exosomes that will potentially be loaded with therapeutic agents. Some techniques for the purification of isolated exosomes include field flow fractionation and sucrose density gradient centrifugation.  Standardized methods for isolating and/or purifying exosomes from biological samples do not exist and this is a critical research gap that has been recognized by the International Society for Extracellular Vesicles (3). This postdoctoral solicitation features an opportunity to address this urgent need by inviting motivated investigators to comprehensively examine and expand upon current methods or to develop completely new, reproducible methods for isolating, purifying and characterizing exosomes from biological samples.  Method development efforts should focus on the incorporation of a robust and optimized experimental design aimed at assessing the sources of variability, repeatability and reproducibility for isolating and purifying exosomes from a representative biological model.  Measurements should incorporate the use of process controls, rigorous statistical analysis techniques and method robustness evaluations appropriate for high-quality protocol development.

References:

(1) Pegtel, D.M., Gould, S.J. (2019) Exosomes. Annu Rev Biochem 88, 487-514.

(2) Patel, G.K., Khan, M.A., Zubair, H., Srivastava, S.K., Khusman, M., Singh, S., Singh, A.P. (2019) Comparative analysis of exosome isolation methods using culture supernatant for optimum yield, purity and downstream applications. Sci Rep 9.

(3) Lotvall, J., Hill, A.F., Hochberg, F., Buzas, E.I., Di Vizio, D., Gardiner, C., Gho, Y.S., Kurochkin, I.V., et al (2014) Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles. J. Extracell Vesicles 3, 26913.

Keywords:
characterization; drug delivery, exosomes; extracellular vesicles; isolation; measurement assurance; method development; microvesicles; therapeutics

Eligibility

Citizenship:  Open to U.S. citizens
Level:  Open to Postdoctoral applicants

Stipend

Base Stipend Travel Allotment Supplementation
$72,030.00 $3,000.00
Copyright © 2014. National Academy of Sciences. All rights reserved. 500 Fifth St. N.W., Washington, D.C. 20001.
Terms of Use and Privacy Statement.