Adeno-associated virus-based gene therapy treats inflammatory kidney disease in mice
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Adeno-associated virus-based gene therapy treats inflammatory kidney disease in mice. / Wu, Guochao; Liu, Shuya; Hagenstein, Julia; Alawi, Malik; Hengel, Felicitas E; Schaper, Melanie; Akyüz, Nuray; Liao, Zhouning; Wanner, Nicola; Tomas, Nicola M; Failla, Antonio Virgilio; Dierlamm, Judith; Körbelin, Jakob; Lu, Shun; Huber, Tobias B.
in: J CLIN INVEST, Jahrgang 134, Nr. 17, 15.08.2024.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Adeno-associated virus-based gene therapy treats inflammatory kidney disease in mice
AU - Wu, Guochao
AU - Liu, Shuya
AU - Hagenstein, Julia
AU - Alawi, Malik
AU - Hengel, Felicitas E
AU - Schaper, Melanie
AU - Akyüz, Nuray
AU - Liao, Zhouning
AU - Wanner, Nicola
AU - Tomas, Nicola M
AU - Failla, Antonio Virgilio
AU - Dierlamm, Judith
AU - Körbelin, Jakob
AU - Lu, Shun
AU - Huber, Tobias B
PY - 2024/8/15
Y1 - 2024/8/15
N2 - Adeno-associated virus (AAV) is a promising in vivo gene delivery platform showing advantages in delivering therapeutic molecules to difficult or undruggable cells. However, natural AAV serotypes have insufficient transduction specificity and efficiency in kidney cells. Here, we developed an evolution-directed selection protocol for renal glomeruli and identified what we believe to be a new vector termed AAV2-GEC that specifically and efficiently targets the glomerular endothelial cells (GEC) after systemic administration and maintains robust GEC tropism in healthy and diseased rodents. AAV2-GEC-mediated delivery of IdeS, a bacterial antibody-cleaving proteinase, provided sustained clearance of kidney-bound antibodies and successfully treated antiglomerular basement membrane glomerulonephritis in mice. Taken together, this study showcases the potential of AAV as a gene delivery platform for challenging cell types. The development of AAV2-GEC and its successful application in the treatment of antibody-mediated kidney disease represents a significant step forward and opens up promising avenues for kidney medicine.
AB - Adeno-associated virus (AAV) is a promising in vivo gene delivery platform showing advantages in delivering therapeutic molecules to difficult or undruggable cells. However, natural AAV serotypes have insufficient transduction specificity and efficiency in kidney cells. Here, we developed an evolution-directed selection protocol for renal glomeruli and identified what we believe to be a new vector termed AAV2-GEC that specifically and efficiently targets the glomerular endothelial cells (GEC) after systemic administration and maintains robust GEC tropism in healthy and diseased rodents. AAV2-GEC-mediated delivery of IdeS, a bacterial antibody-cleaving proteinase, provided sustained clearance of kidney-bound antibodies and successfully treated antiglomerular basement membrane glomerulonephritis in mice. Taken together, this study showcases the potential of AAV as a gene delivery platform for challenging cell types. The development of AAV2-GEC and its successful application in the treatment of antibody-mediated kidney disease represents a significant step forward and opens up promising avenues for kidney medicine.
KW - Animals
KW - Dependovirus/genetics
KW - Mice
KW - Genetic Therapy/methods
KW - Genetic Vectors/genetics
KW - Humans
KW - Endothelial Cells/metabolism
KW - Kidney Glomerulus/pathology
KW - Glomerulonephritis/therapy
KW - Anti-Glomerular Basement Membrane Disease/therapy
U2 - 10.1172/JCI174722
DO - 10.1172/JCI174722
M3 - SCORING: Journal article
C2 - 39225099
VL - 134
JO - J CLIN INVEST
JF - J CLIN INVEST
SN - 0021-9738
IS - 17
ER -
