# Targeted cell-to-cell mRNA delivery of therapeutic circuits

> **NIH NIH F30** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2023 · $52,694

## Abstract

Project Summary
mRNA holds great therapeutic potential as an agent to induce expression of proteins in cells. Precise delivery of
mRNA to diseased cell types could have numerous applications, from correcting pathogenic mutations by gene
editing to inducing killing in diseased cell types to cell state reprogramming. Despite this potential, it remains
challenging to deliver mRNA to specific subsets of cells. A general method to safely deliver mRNA cargo to
target cell types within a patient’s body would unlock the full therapeutic potential of mRNA. Living cells are ideal
delivery vehicles because they can be programmed to use sensing and logic to specifically deliver mRNA to
target cell populations.
Towards this goal, our lab has recently developed delivery cells capable of exporting mRNA in synthetic export
vehicles (synEVs). These particles can transfer mRNA cargo to receiver cells, where it is expressed. In this
proposal, we aim to create, optimize, and integrate elements to generate an ideal cell-based mRNA delivery
platform. In Aim 1, we will engineer primary human T cells, a clinically relevant cell type, as delivery cells. In Aim
2, we will develop strategies to control targeting specificity by engineering conditional sending and pseudotyping.
In Aim 3, we will demonstrate cell-cell delivery and functionality of mRNA in vivo by delivering a circuit that
induces cell death to tumor cells, which should bypass the immunosuppression that limits traditional immune
cell-based therapies.
Together, this work will expand our capabilities in cell-cell mRNA delivery and enable a novel, cell-based tumor
killing strategy that circumvents immunosuppression. Further, while we focus on applications related to cancer
in this proposal, this work will establish a platform with broad utility across biomedicine, including for in vivo cell
reprogramming and genome editing.

## Key facts

- **NIH application ID:** 10827328
- **Project number:** 1F30OD036190-01
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Victoria Rose Tobin
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $52,694
- **Award type:** 1
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10827328

## Citation

> US National Institutes of Health, RePORTER application 10827328, Targeted cell-to-cell mRNA delivery of therapeutic circuits (1F30OD036190-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10827328. Licensed CC0.

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