Alginate hydrogel polymers enable efficient delivery of a vascular-targeted AAV vector into aortic tissue

Molecular Therapy: Methods & Clinical Development

Laura Kummer¹  Dima Ibrahim Basha²  Christopher Borowski²  Georg Lutter²  Markus Hecker²  Derk Frank³  Marcin Zaradzki⁴  Norbert Frey⁵  Rawa Arif⁵  Thomas Puehler⁶  Jasmin Soethoff⁶  Anca Remes⁶  Andreas H. Wagner⁶  Susanne Hille⁷  Oliver J. Müller⁷ 

[1] Department of Cardiac and Vascular Surgery, University of Kiel, Kiel, Germany;German Centre for Cardiovascular Research, Partner Site Hamburg/Kiel/Lübeck, Germany;Department of Anesthesiology, University Hospital Heidelberg, Heidelberg, Germany;Department of Cardiac Surgery, University Hospital Heidelberg, Heidelberg, Germany;Department of Cardiovascular Physiology, Heidelberg University, Heidelberg, Germany;Department of Internal Medicine III, University of Kiel, Kiel, Germany;German Centre for Cardiovascular Research, Partner Site Hamburg/Kiel/Lübeck, Germany;

关键词: alginate hydrogel;    adeno-associated virus;    AAV vector;    vascular gene transfer;    aorta;    gene therapy;   

DOI  :  

来源: DOAJ

【 摘 要 】

Gene therapeutic approaches to aortic diseases require efficient vectors and delivery systems for transduction of endothelial cells (ECs) and smooth muscle cells (SMCs). Here, we developed a novel strategy to efficiently deliver a previously described vascular-specific adeno-associated viral (AAV) vector to the abdominal aorta by application of alginate hydrogels. To efficiently transduce ECs and SMCs, we used AAV9 vectors with a modified capsid (AAV9SLR) encoding enhanced green fluorescent protein (EGFP), as wild-type AAV vectors do not transduce ECs and SMCs well. AAV9SLR vectors were embedded into a solution containing sodium alginate and polymerized into hydrogels. Gels were surgically implanted around the adventitia of the infrarenal abdominal aorta of adult mice. Three weeks after surgery, an almost complete transduction of both the endothelium and tunica media adjacent to the gel was demonstrated in tissue sections. Hydrogel-mediated delivery resulted in induction of neutralizing antibodies but did not cause inflammatory responses in serum or the aortic wall. To further determine the translational potential, aortic tissue from patients was embedded ex vivo into AAV9SLR-containing hydrogel, and efficient transduction could be confirmed. These findings demonstrate that alginate hydrogel harboring a vascular-targeting AAV9SLR vector allows efficient local transduction of the aortic wall.

【 授权许可】

Unknown