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Opportunity at National Institute of Standards and Technology (NIST)

Structural Profiling of mRNA Vaccine and Therapeutic Platform Technologies

Location

Material Measurement Laboratory, Biomolecular Measurement Division

RO# Location
50.64.51.C0475 Gaithersburg, MD

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

Advisers

Name E-mail Phone
Brinson, Robert Goodwin robert.brinson@nist.gov 240.314.6336
Cleveland, Thomas Edgar thomas.cleveland@nist.gov 240.314.6283
Marino, John P. john.marino@nist.gov 240.314.6160

Description

A promising platform for rapid vaccine and therapeutic development involves the use of packaged messenger RNAs (mRNAs) that can be delivered to a patient, whose own cellular machinery then produces the antigenic protein or biotherapeutic drug from the mRNA sequence. In principle, such vaccines and biotherapeutics can be quickly adapted to new disease organisms simply by substituting a new mRNA sequence, making them ideal tools for combatting emerging epidemics. The development of mRNA vaccines and biotherapeutics has increased dramatically as past problems, such as instability from cellular degradation, immunogenic responses, and delivery problems, have been greatly ameliorated by recent technological advances. These have included the introduction of modified nucleosides, engineering of the untranslated regions (UTR), and development of lipid nanoparticle (LNP) encapsulation. However, the impact of mRNA structure in the context of different UTRs, open reading frames and lipid formulation on the safety and efficacy of these vaccines remains an open question. In addition, the interchangeability of different mRNA sequences with respect to the structure of the LNP has not been fully demonstrated. To address these issues, a multi-modal approach will be taken, in which cryogenic electron microscopy (CryoEM) and scattering techniques (SAXS and SANS) will be combined with other biophysical and chemical footprinting approaches (e.g., SHAPE), in an effort to establish and harmonize methods for structural profiling of mRNA vaccines. These methods will be taken together to determine ‘best practices’ to meet the rigorous assessment and quality assurance required by the pharmaceutical industry.

Keywords:
mRNA; platform; structure profiling; vaccines; biotherapeutics; lipid nanoparticle; cryoEM; SAXS; SANS; chemical foot-printing; SHAPE

Eligibility

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

Stipend

Base Stipend Travel Allotment Supplementation
$72,030.00 $3,000.00
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