Nucleic Acid Delivery to the Vascular Endothelium

Mol Pharm. 2022 Dec 5;19(12):4466-4486. doi: 10.1021/acs.molpharmaceut.2c00653. Epub 2022 Oct 17.


This Review examines the state-of-the-art in the delivery of nucleic acid therapies that are directed to the vascular endothelium. First, we review the most important homeostatic functions and properties of the vascular endothelium and summarize the nucleic acid tools that are currently available for gene therapy and nucleic acid delivery. Second, we consider the opportunities available with the endothelium as a therapeutic target and the experimental models that exist to evaluate the potential of those opportunities. Finally, we review the progress to date from investigations that are directly targeting the vascular endothelium: for vascular disease, for peri-transplant therapy, for angiogenic therapies, for pulmonary endothelial disease, and for the blood-brain barrier, ending with a summary of the future outlook in this field.

Keywords: endothelium; nanoparticle; nonviral vehicle; nucleic acid delivery; polymeric vehicle; polyplex.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Biological Transport
  • Blood-Brain Barrier
  • Endothelium, Vascular
  • Genetic Therapy
  • Nucleic Acids* / genetics


  • Nucleic Acids