# New Materials to Deliver mRNA: Applications in Cancer Immunotherapy

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $514,997

## Abstract

Project Summary: Cancer is a leading global cause of mortality. The goal of this multi-disciplinary
project is to pre-clinically advance a novel concept for selective and efficient mRNA delivery that enables a
highly promising vaccination strategy for cancer immunotherapy. Given the potential of cancer vaccination
to both generate new antigen-specific T cell responses against tumor cells and amplify existing responses,
cancer vaccination could be an especially effective therapy on its own or in combination with, e.g., check-
point blockade. Through a unique collaboration of chemists, cancer immunologists and biostatisticians we
propose to advance just such a method called CART-RNA which in preliminary studies has produced
cures of up to 80% in animals with established tumors.
 The critical technological challenge for mRNA and all gene-based therapies is the development of
safe, effective, accessible and selective mRNA delivery vectors. This project exploits a unique class of
charge-altering releasable transporters (CARTs) that complex, protect and selectively deliver mRNA to
target cells/organs and then release mRNA intracellularly through an unprecedented charge-altering
mechanism, mediating exceptionally effective translation to proteins both in cell culture and in live animals.
 The three interrelated specific aims are directed at the design and evaluation of novel CARTs that
deliver mRNA to a variety of cell types, elicit functional protein expression, and induce a therapeutic
immunological response. Aim 1 leverages the synthetic expertise of the team and the ease of formulation
of CART-RNA vectors to assess the relationship of CART chemical structure, formulation and
administration to the efficiency and selectivity of protein expression in culture and in live animals. Aim 2 is
directed at the evaluation of CART-RNA vaccination to elicit protective immunological responses in
validated mouse models for cancer immunotherapy. Aim 3 focuses on pre-clinical investigations to elicit
protective immunity against clinically-relevant antigens (specifically B- and T-cell lymphoma idiotypes) in
primary human cells from human patients.
 This project exploits an interdisciplinary approach that integrates materials design and synthesis,
chemistry, microbiology, non-invasive cellular and live animal imaging, immunology and biostatistics to
develop, evaluate and refine strategies for the development of novel vaccines based on the new CART-
RNA platform. Cellular and live animal imaging techniques will be employed to assess the efficiency of
both mRNA delivery and expression as a function of mode of administration in mice. This research will
identify and clarify design criteria for engineering effective mRNA delivery systems and the effectiveness
of mRNA-based approaches for immunotherapy. This project is directed at new families of superior
transfecting agents for mRNA delivery and mRNA vaccination for treating and curing cancer.

## Key facts

- **NIH application ID:** 10620636
- **Project number:** 5R01CA245533-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** RONALD LEVY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $514,997
- **Award type:** 5
- **Project period:** 2020-08-13 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10620636

## Citation

> US National Institutes of Health, RePORTER application 10620636, New Materials to Deliver mRNA: Applications in Cancer Immunotherapy (5R01CA245533-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10620636. Licensed CC0.

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