Alginate hydrogel polymers enable efficient delivery of a vascular-targeted AAV vector into aortic tissue.
AAV vector
adeno-associated virus
alginate hydrogel
aorta
endothelial cells
gene therapy
smooth muscle cells
vascular disease
vascular gene transfer
vascular system
Journal
Molecular therapy. Methods & clinical development
ISSN: 2329-0501
Titre abrégé: Mol Ther Methods Clin Dev
Pays: United States
ID NLM: 101624857
Informations de publication
Date de publication:
11 Jun 2021
11 Jun 2021
Historique:
received:
22
06
2020
accepted:
19
02
2021
entrez:
26
3
2021
pubmed:
27
3
2021
medline:
27
3
2021
Statut:
epublish
Résumé
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
Identifiants
pubmed: 33768132
doi: 10.1016/j.omtm.2021.02.017
pii: S2329-0501(21)00032-2
pmc: PMC7973147
doi:
Types de publication
Journal Article
Langues
eng
Pagination
83-93Informations de copyright
© 2021 The Author(s).
Déclaration de conflit d'intérêts
O.J.M. has previously filed a patent application on the vascular-targeted AAV9SLR capsid variant. The other authors declare no competing interests.
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