# Advancing mRNA Vaccines for Cancer Therapy Using Molecularly Barcoded Nanotechnology

> **NIH NIH F32** · UNIVERSITY OF PENNSYLVANIA · 2020 · $9,473

## Abstract

PROJECT SUMMARY
Recent advances in genome sequencing has enabled the detection of random somatic mutations, or
neoantigens, in cancer cells from individual patient samples. Thus, neoantigens are ideal targets for
cancer vaccination because they avoid harmful toxicities to healthy cells, and they are personalized
based on patient samples. For successful vaccination, mRNA molecules need to be delivered to
dendritic cells in the lymph nodes and spleen, which then present the antigen to T cells. This results in
antigen-specific T cell activation that enables them to recognize cancer cells expressing the neoantigen
of interest. However, the use of mRNA for vaccination is limited by molecular instability, in vivo delivery
barriers, and insufficient T cell activation. The main goal of this proposal is to develop lipid nanoparticles
(LNPs) to deliver neoantigen mRNA vaccines to DCs in vivo. LNPs improve upon mRNA delivery by
protecting the molecules from degradation, enabling their cellular uptake, and providing tissue- and
cell-specific accumulation. However, it is not well understood how LNP chemical composition and
physical properties influence mRNA delivery to the lymph nodes, spleen, and to specific immune cell
populations. Developing LNPs specifically for mRNA delivery is challenging because (i) only one LNP
can be evaluated in a mouse at a time, and (ii) results evaluating cellular uptake of LNPs in vitro does
not indicate in vivo results. This proposal will utilize high throughput molecular barcoding technology to
screen a library of LNPs simultaneously in a single mouse. This will enable us to identify key
structure:function relationships between LNP design and delivery, and it will provide LNPs that elicit
strong immune responses for neoantigen vaccine delivery. Thus, I hypothesize that molecular
barcoding will predict the LNP designs that yield the strongest antigen-specific T cell responses to treat
cancer. In Aim 1, I will develop and evaluate molecular barcoding nanotechnology to assess LNP
delivery to immune cells, and particular subtypes of dendritic cells, in the lymph nodes and spleens in
vivo. In Aim 2, I will use the top-performing LNPs to deliver neoantigen vaccines and elicit the
maturation of dendritic cells and activation of T cells to treat a mouse model of colon cancer. Moving
forward, these highly modular platforms can be used to deliver multiple neoantigen mRNAs
simultaneously, and they can be used as tools for studying the underlying immunobiology of specific
populations of immune cells towards improving cancer vaccination.

## Key facts

- **NIH application ID:** 10068326
- **Project number:** 1F32CA243475-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Rachel Riley
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $9,473
- **Award type:** 1
- **Project period:** 2020-07-01 → 2020-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10068326

## Citation

> US National Institutes of Health, RePORTER application 10068326, Advancing mRNA Vaccines for Cancer Therapy Using Molecularly Barcoded Nanotechnology (1F32CA243475-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10068326. Licensed CC0.

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