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In Vivo Gene Transfer to the Rabbit Common Carotid Artery Endothelium
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Advances in endothelial cell targeting by AAV vectors.

Milena Cichon1,2, Alicja Jozkowicz1, Anna Grochot-Przeczek1

  • 1Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.

Acta Biochimica Polonica
|February 25, 2026
PubMed
Summary

Researchers are engineering adeno-associated virus (AAV) vectors to improve gene delivery targeting endothelial cells (ECs). This enhances potential for treating vascular diseases.

Keywords:
AAVadeno-associated virusblood vesselsendothelial cellsgene therapy

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Area of Science:

  • * Gene Therapy
  • * Molecular and Cellular Biology
  • * Biotechnology

Background:

  • * Adeno-associated virus (AAV) vectors are crucial for *in vivo* gene delivery but show limited transduction of endothelial cells (ECs) after systemic administration.
  • * This tropism barrier hinders gene therapies for cardiovascular, neurovascular, and inflammatory conditions.
  • * Targeting ECs is essential for effective vascular gene therapies.

Purpose of the Study:

  • * To review strategies for redirecting AAV tropism toward endothelial cells.
  • * To highlight advances in genetic capsid engineering, peptide display, and non-genetic surface modifications for EC targeting.
  • * To discuss the potential of modified AAVs for precise vascular gene therapies.

Main Methods:

  • * Review of recent literature on AAV capsid engineering for EC tropism.
  • * Analysis of strategies including peptide incorporation, genetic modifications to reduce HSPG binding, and polymer-coating.
  • * Examination of AAV4 serotype's unique endothelial tropism via O-linked sialic acid recognition.

Main Results:

  • * AAV4 serotype demonstrates significant, previously underappreciated, endothelial tropism.
  • * Engineered AAV capsids with EC-binding peptides enhance vascular targeting in specific beds.
  • * Strategies reducing heparan sulfate proteoglycan (HSPG) binding improve EC transduction and reduce hepatocyte uptake.
  • * Polymer-coating enables receptor-specific EC targeting and reduces immunogenicity.

Conclusions:

  • * Genetic and non-genetic capsid modifications can effectively redirect AAV tropism to endothelial cells.
  • * Targeted AAV vectors show promise for overcoming delivery barriers in vascular gene therapy.
  • * Advances in AAV engineering are crucial for developing precise and efficient vascular gene therapies.