Systemic Vascular Transduction by Capsid Mutant Adeno-Associated Virus After Intravenous Injection. Hum Gene Ther 2015 Nov;26(11):767-76
Date
09/12/2015Pubmed ID
26359319Pubmed Central ID
PMC4651034DOI
10.1089/hum.2015.097Scopus ID
2-s2.0-84946906911 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
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.
Author List
Lipinski DM, Reid CA, Boye SL, Peterson JJ, Qi X, Boye SE, Boulton ME, Hauswirth WWAuthor
Daniel M. Lipinski PhD Associate Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Administration, IntravenousAnimals
Capsid Proteins
Dependovirus
Endothelial Cells
Genetic Therapy
Genetic Vectors
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mutation
Transduction, Genetic
Vascular Diseases
