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Targeted cell-to-cell mRNA delivery of therapeutic circuits

Award Number: F30OD036190
ORGANIZATION: OFFICE OF THE DIRECTOR, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $55,114 )
2026	2026	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Research Infrastructure Programs	000	4	8/28/2026	NON-COMPETING CONTINUATION	$55,114
														Subtotal = $55,114

Issue Date FY: 2025 ( Subtotal = $54,538 )
2025	2025	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Research Infrastructure Programs	000	3	8/4/2025	NON-COMPETING CONTINUATION	$54,538
														Subtotal = $54,538

Issue Date FY: 2024 ( Subtotal = $53,974 )
2024	2024	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Research Infrastructure Programs	000	2	8/13/2024	NON-COMPETING CONTINUATION	$53,974
														Subtotal = $53,974

Issue Date FY: 2023 ( Subtotal = $52,694 )
2023	2023	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Research Infrastructure Programs	001	1	8/31/2023	NEW	$0
2023	2023	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Research Infrastructure Programs	000	1	8/31/2023	NEW	$52,694
														Subtotal = $52,694

Grand Total All Awards = $216,320

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Targeted cell-to-cell mRNA delivery of therapeutic circuits

Award Number: F30OD036190

ORGANIZATION: OFFICE OF THE DIRECTOR, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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