# Manufacturing and Characterization of Potent mRNA Lipid Nanoparticle Vaccines at Multiple Scales

> **NIH FDA R01** · GEORGE MASON UNIVERSITY · 2021 · $498,998

## Abstract

PROJECT SUMMARY
mRNA vaccines have received emergency authorization approval for Covid-19 and are under development for
several other infectious diseases. The mRNA-encoded immunogen in these vaccines is delivered inside a lipid
nanoparticle (LNP) that comprises four lipids, the most important being the ionizable lipid that is responsible for
releasing the mRNA from intracellular endosomes through protonation of amine groups that interact with the
endosomal membrane. Clinical studies showed these vaccines are highly efficacious with over 94% of patients
protected from SARS-CoV-2 infection. Although the successful development of mRNA LNP vaccines for SARS-
Cov-2 constitutes a major breakthrough for a novel medical modality, it has also highlighted several unanswered
questions surrounding this platform that require urgent investigation including : 1) What are the critical features
of mRNA LNP manufacturing that need to be respected to create potent systems ? 2) What is functional
consequence of truncated mRNA transcripts produced by in vitro translation (IVT) or by degradation and how
can they be minimized through IVT optimization ? 3) What causes degradation of mRNA LNPs during
manufacturing and storage and how can this be measured and minimized ?
We recently discovered a new process to rationally design ionizable lipids for increased potency. We also
discovered a novel manufacturing process to assemble the mRNA LNP such that the same lipid and mRNA
components produce a much more efficient and potent delivery system. This allows more of the mRNA in the
LNP to be translated thereby reducing dose and reactogenicity and increasing the number of people that can be
vaccinated with the same quantity of vaccine. We have initiated studies to characterize and understand mRNA
LNP stability that can affect the quality and performance of these vaccines. In this proposal we will perform
studies to further the understanding of how mRNA LNPs are assembled and manufactured at different
manufacturing scales from laboratory scale to commercial scale. The lack of public information in this area is a
major impediment to improving and broadening the use of this new vaccine modality. We will also illuminate the
presence and importance of the heterogeneity of different transcripts in the mRNA drug substance and how that
heterogeneity could impact product performance. And finally, the stability of mRNA LNPs during manufacturing
and storage will be studied to understand the degradation mechanisms causing loss of bioactivity and structural
integrity of the mRNA and lipids, how to measure these properties, and develop formulations that have extended
stability profiles compared to current products.

## Key facts

- **NIH application ID:** 10407326
- **Project number:** 1R01FD007457-01
- **Recipient organization:** GEORGE MASON UNIVERSITY
- **Principal Investigator:** MIKELL PAIGE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2021
- **Award amount:** $498,998
- **Award type:** 1
- **Project period:** 2021-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10407326

## Citation

> US National Institutes of Health, RePORTER application 10407326, Manufacturing and Characterization of Potent mRNA Lipid Nanoparticle Vaccines at Multiple Scales (1R01FD007457-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10407326. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*