# A Bio-orthogonal Targeting System for Precision Drug Delivery to Vascular Endothelium in Transplanted Organs

> **NIH NIH F30** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2024 · $53,974

## Abstract

Project Summary and Abstract.
The viability of a transplanted organ and the patient’s health are inherently limited by the burdens of
immunosuppressive therapy, which must be used for the duration of the patient’s life. Systemic administration
of these immunosuppressive agents increases the incidence of infectious disease and malignancy, which are
the leading causes of death in transplant patients. While new tolerance induction strategies are evolving, like
Treg therapies and mixed chimerism, they are limited in their ability to only be used for living donor transplants
and difficulties in ex vivo culture and expansion. However, developments in the field of ex vivo machine
perfusion of transplanted organs now offer unique therapeutic opportunities to treat donor organs prior to their
implantation into the recipient. My work focuses on creating a system that leverages advances in ex vivo
perfusion to install a bio-orthogonal surface targeting moiety on an organ, which is introduced to the organ via
ex vivo perfusion during its time in transport. I hypothesize that this targeting system will allow for the
systemic dosing of lipid nanoparticles that bind only to vascular endothelium expressing the bio-
orthogonal target within the organ, therefore allowing for localized immunosuppression and immune
tolerance induction, while minimizing the highly undesirable and toxic side effects of
immunosuppressive drugs. Aim 1 of this proposal demonstrates the targeted drug delivery to vascular
endothelium via lipid nanoparticle binding to permanently expressed bio-orthogonal moiety in two dimensional
endothelial culture. Aim 2 includes the optimization and demonstration of the LNP targeting system to
effectively deliver therapeutic cargo under physiological sheer stress and flow conditions. This will be
performed in ex vivo perfused human blood vessels. Aim 3 harnesses the ability of the system to be utilized in
a relevant heterotopic murine heart transplantation model as a proof-of-concept to demonstrate the ability for
the targeted particles to localized to a transplanted organ.
 This proposal builds around four key components of critical research and clinical skills to support my
development into an independent physician scientist: (1) an interdisciplinary research project focusing on a
novel nucleic acid delivery system for the selective delivery of therapeutics to a transplanted organ (2) multi-
disciplinary mentoring from Drs. Grinstaff (biomaterials, nanoparticles, drug delivery) and Osho (clinical
medicine, animal models, and ex vivo perfusion), (3) academic physician scientist training in research
conduct and communication skills, (4) clinical awareness program, overseen by Dr. Osho a na�onally recognized
leader in the field. (5) professional development to guide my training goals.

## Key facts

- **NIH application ID:** 10998558
- **Project number:** 1F30HL176145-01
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Aria Pearlman Morales
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 1
- **Project period:** 2024-09-30 → 2029-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10998558

## Citation

> US National Institutes of Health, RePORTER application 10998558, A Bio-orthogonal Targeting System for Precision Drug Delivery to Vascular Endothelium in Transplanted Organs (1F30HL176145-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10998558. Licensed CC0.

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