Systemic Vascular Transduction by Capsid Mutant Adeno-Associated Virus After Intravenous Injection

Hum Gene Ther. 2015 Nov;26(11):767-76. doi: 10.1089/hum.2015.097. Epub 2015 Sep 29.


The ability to effectively deliver genetic material to vascular endothelial cells remains one of the greatest unmet challenges facing the development of gene therapies to prevent diseases with underlying vascular etiology, such as diabetes, atherosclerosis, and age-related macular degeneration. Herein, we assess the effectiveness of an rAAV2-based capsid mutant vector (Y272F, Y444F, Y500F, Y730F, T491V; termed QuadYF+TV) with strong endothelial cell tropism at transducing the vasculature after systemic administration. Intravenous injection of QuadYF+TV resulted in widespread transduction throughout the vasculature of several major organ systems, as assessed by in vivo bioluminescence imaging and postmortem histology. Robust transduction of lung tissue was observed in QuadYF+TV-injected mice, indicating a role for intravenous gene delivery in the treatment of chronic diseases presenting with pulmonary complications, such as α1-antitrypsin deficiency. The QuadYF+TV vector cross-reacted strongly with AAV2 neutralizing antibodies, however, indicating that a targeted delivery strategy may be required to maximize clinical translatability.

Publication types

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

MeSH terms

  • Administration, Intravenous*
  • Animals
  • Capsid Proteins / genetics
  • Dependovirus / genetics
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism*
  • Genetic Therapy*
  • Genetic Vectors / administration & dosage*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mutation
  • Transduction, Genetic*
  • Vascular Diseases / genetics
  • Vascular Diseases / therapy*


  • Capsid Proteins