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Related Experiment Video

Updated: Jan 22, 2026

Isolation and Culture Expansion of Tumor-specific Endothelial Cells

Isolation and Culture Expansion of Tumor-specific Endothelial Cells

Published on: October 14, 2015

Targeting DNA-LNPs to Endothelial Cells Improves Expression Magnitude, Duration, and Specificity.

Nicolas Marzolini¹, Taylor V Brysgel², Ryan J Rahman³

¹Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)

|January 20, 2026

Summary

Targeted DNA-lipid nanoparticles (DNA-LNPs) show improved organ specificity for gene delivery. This advance offers a promising therapeutic platform for endothelial-centric diseases.

Keywords:

DNA drug delivery systems drug targeting endothelium nanoparticles

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Area of Science:

Biotechnology
Nanomedicine
Gene Therapy

Background:

DNA-lipid nanoparticles (DNA-LNPs) are effective for in vivo DNA delivery.
Targeting specific organs can enhance therapeutic efficacy and reduce side effects.
Current methods lack precise control over DNA-LNP biodistribution.

Purpose of the Study:

To develop extrahepatic DNA-LNP targeting strategies.
To enhance organ- and cell-type-specific transgene expression.
To establish a therapeutic platform for endothelial-centric diseases.

Main Methods:

Conjugating DNA-LNPs with antibodies against PECAM-1 (lungs) and VCAM-1 (brain/spleen).
Evaluating transgene expression in target organs compared to untargeted LNPs.
Utilizing Fab fragments to improve targeting specificity.
Performing single-cell analysis to understand expression mechanisms.

Main Results:

PECAM-1 and VCAM-1 targeted DNA-LNPs achieved robust, long-lasting transgene expression in target organs.
Lung-specific expression increased over time, showing higher lung-to-liver ratios than previous mRNA-LNPs.
Replacing antibodies with Fab fragments further improved organ specificity.
Endothelial cells in target organs were key for sustained expression, unlike off-target liver cells.

Conclusions:

Targeted DNA-LNPs enable precise organ- and cell-type-specific gene delivery.
This technology offers a potential therapeutic strategy for numerous endothelial-related diseases.
The findings pave the way for advanced nanomedicine applications in gene therapy.