# A New Lipid Nanoparticle Technology Enabling Long-acting mRNA Therapy

> **NIH NIH R33** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $513,877

## Abstract

ABSTRACT
Recent clinical success of mRNA vaccines for COVID-19 has sparked enormous interest in mRNA therapy for a
wide range of biomedical applications including protein replacement therapy. However, one unique challenge
associated with mRNA therapy is dealing with the transient efficacy due to its relatively short half-life. Current
nanoparticles including FDA-approved lipid nanoparticles (LNPs) could significantly improve mRNA translation
efficiency, but the duration of in vivo protein expression by these mRNA NPs is generally short (limited to a few
days), thus requiring frequent re-dosing. The main objective of this project is to advance a new transformative
LNP technology enabling long-acting mRNA replacement therapy of genetic disorders associated with loss of
function of a particular protein. In our recent studies, we developed a new generation of LNPs and performed
the head-to-head comparison in vitro and in vivo to the benchmark LNP formulations composed of FDA-approved
ionizable lipids. We observed a dramatic increase of the duration of model protein expression in vitro and in vivo
by our new mRNA LNPs. Preliminary safety studies showed that our mRNA LNPs were well tolerated without
observable adverse events in vivo. With the proof-of-concept demonstration of our long-acting mRNA LNPs, this
project aims to i) further optimize the mRNA LNP technology for longer-term, high level protein expression, and
ii) rigorously validate this transformative mRNA delivery platform using hemophilia A as a model disease. We
expect that with successful validation in normal and hemophilia A mice, this long-acting mRNA LNP platform
could be readily moved into clinical testing for hemophilia and expanded to other genetic diseases that require
restoration of normal protein functions.

## Key facts

- **NIH application ID:** 10867446
- **Project number:** 5R33HL168751-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Jinjun Shi
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $513,877
- **Award type:** 5
- **Project period:** 2023-06-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10867446

## Citation

> US National Institutes of Health, RePORTER application 10867446, A New Lipid Nanoparticle Technology Enabling Long-acting mRNA Therapy (5R33HL168751-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10867446. Licensed CC0.

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