Targeted mRNA delivery through lung blood vessels.

mRNA Targeted Drug Delivery: Revolutionizing Treatment with Precision Medicine

Elliot Brynn in Health & Wellness August 2025 • 4 min read.

"A New Era of Targeted Therapies: How Directing mRNA to Specific Cells Can Enhance Drug Delivery and Expression"

Messenger RNA (mRNA) therapeutics have emerged as a promising alternative to traditional treatments, offering innovative solutions in fields like vaccination, protein replacement, and cellular reprogramming. These mRNA-based approaches use synthetic mRNA to instruct cells to produce specific proteins, addressing deficiencies or combating diseases directly at the cellular level.

A significant challenge in mRNA therapeutics is ensuring that the mRNA reaches the intended target cells efficiently. Systemic administration often leads to the mRNA being taken up predominantly by the liver, limiting its effectiveness in treating other organs or tissues. To overcome this, researchers are developing targeted delivery systems that can direct mRNA to specific cell types, enhancing therapeutic outcomes and minimizing off-target effects.

One such innovative approach involves re-targeting exogenous mRNA to the lungs by directing it via PECAM-1, a molecule expressed on blood vessel cells. This method enhances vascular delivery and gene expression in the lungs, independently of apolipoprotein E-mediated uptake, marking a significant advancement in targeted drug delivery.

How Does PECAM-1 Targeting Enhance mRNA Delivery?

Targeted mRNA delivery through lung blood vessels.

The key to this innovative approach lies in modifying lipid nanoparticles (LNPs), which are used to encapsulate and deliver the mRNA. By conjugating these LNPs with antibodies specific to PECAM-1 (Platelet Endothelial Cell Adhesion Molecule-1), researchers can guide the mRNA directly to the cells lining the blood vessels in the lungs. PECAM-1 is highly expressed on endothelial cells, making it an ideal target for directing therapeutics to the pulmonary vasculature.

This targeted approach offers several advantages over traditional methods. First, it significantly enhances the delivery of mRNA to the lungs while reducing uptake in the liver. Studies have shown a remarkable increase in mRNA delivery and protein expression in the lungs—approximately 200-fold and 25-fold, respectively—compared to non-targeted LNPs. This means more of the therapeutic mRNA reaches its intended destination, leading to better treatment outcomes.

Enhanced Lung Delivery: Increases mRNA and protein expression in the lungs.
Reduced Liver Uptake: Minimizes off-target effects by decreasing liver accumulation.
Apolipoprotein E Independence: Operates independently of traditional mRNA uptake pathways, enhancing versatility.
Vascular Targeting: Precisely directs mRNA to blood vessel cells in the lungs.

Another critical benefit is that this delivery method operates independently of apolipoprotein E (apoE), a protein that typically mediates the uptake of LNPs by the liver. By bypassing the apoE pathway, the PECAM-1-targeted LNPs can selectively deliver mRNA to the lungs, regardless of the body's natural distribution mechanisms. This is particularly useful because it allows for more controlled and predictable therapeutic outcomes.

The Future of mRNA Therapeutics

Targeting mRNA delivery via PECAM-1 represents a significant leap forward in the field of genetic medicine. By enabling precise control over where and how mRNA is expressed, this approach opens up new possibilities for treating a wide range of pulmonary diseases, from infections to cancer. As research continues and these targeted delivery systems become more refined, we can expect to see even more effective and personalized mRNA therapies in the future.

About this Article -

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This article is based on research published under:

DOI-LINK: 10.1016/j.jconrel.2018.10.015, Alternate LINK

Title: Pecam-1 Directed Re-Targeting Of Exogenous Mrna Providing Two Orders Of Magnitude Enhancement Of Vascular Delivery And Expression In Lungs Independent Of Apolipoprotein E-Mediated Uptake

Subject: Pharmaceutical Science

Journal: Journal of Controlled Release

Publisher: Elsevier BV

Authors: Hamideh Parhiz, Vladimir V. Shuvaev, Norbert Pardi, Makan Khoshnejad, Raisa Yu Kiseleva, Jacob S. Brenner, Thomas Uhler, Steven Tuyishime, Barbara L. Mui, Ying K. Tam, Thomas D. Madden, Michael J. Hope, Drew Weissman, Vladimir R. Muzykantov

Published: 2018-12-01

Everything You Need To Know

What are mRNA therapeutics, and what potential do they offer in treating diseases?

Messenger RNA (mRNA) therapeutics use synthetic mRNA to instruct cells to produce specific proteins. This method can address deficiencies or combat diseases directly at the cellular level. mRNA therapeutics hold promise in vaccination, protein replacement, and cellular reprogramming.

Why is targeted delivery important for mRNA therapeutics, and how do researchers achieve this?

Targeted delivery systems are designed to direct mRNA to specific cell types. This approach enhances therapeutic outcomes and minimizes off-target effects. Researchers modify lipid nanoparticles (LNPs) to achieve targeted delivery.

What is PECAM-1, and how does targeting it enhance mRNA delivery to the lungs?

PECAM-1 (Platelet Endothelial Cell Adhesion Molecule-1) is a molecule expressed on blood vessel cells. By conjugating LNPs with antibodies specific to PECAM-1, researchers can guide mRNA directly to the cells lining the blood vessels in the lungs. This enhances vascular delivery and gene expression in the lungs.

What are the key advantages of targeting mRNA delivery via PECAM-1 compared to traditional methods?

Targeting mRNA delivery via PECAM-1 enhances mRNA and protein expression in the lungs. It also reduces liver uptake, operates independently of apolipoprotein E, and precisely directs mRNA to blood vessel cells in the lungs. It enhances mRNA delivery to the lungs by approximately 200-fold and protein expression by approximately 25-fold compared to non-targeted LNPs.

How does bypassing the apolipoprotein E pathway in mRNA delivery improve therapeutic outcomes, especially in treating pulmonary diseases?

By bypassing the apolipoprotein E pathway, PECAM-1-targeted LNPs can selectively deliver mRNA to the lungs, regardless of the body's natural distribution mechanisms. This is particularly useful because it allows for more controlled and predictable therapeutic outcomes. This approach opens up new possibilities for treating a wide range of pulmonary diseases, from infections to cancer.