Adeno-associated virus-based gene therapy treats inflammatory kidney disease in mice

被引：8

作者：

Wu, Guochao ^{[1
,2
]}

Liu, Shuya ^{[1
,2
]}

Hagenstein, Julia ^{[1
,2
]}

Alawi, Malik ^{[3
]}

Hengel, Felicitas E. ^{[1
,2
]}

Schaper, Melanie ^{[1
,2
]}

Akyuez, Nuray ^{[4
]}

Liao, Zhouning ^{[1
,2
]}

Wanner, Nicola ^{[1
,2
]}

Tomas, Nicola M. ^{[1
,2
]}

Failla, Antonio Virgilio ^{[5
]}

Dierlamm, Judith ^{[4
]}

Koerbelin, Jakob ^{[4
]}

Lu, Shun ^{[1
,2
]}

Huber, Tobias B. ^{[1
,2
]}

机构：

[1] Univ Med Ctr Hamburg Eppendorf, Dept Med 3, Martinistr 52, D-20246 Hamburg, Germany

[2] Univ Med Ctr Hamburg Eppendorf, Hamburg Ctr Kidney Hlth HCKH, Hamburg, Germany

[3] Univ Med Ctr Hamburg Eppendorf, Bioinformat Core, Hamburg, Germany

[4] Univ Med Ctr Hamburg Eppendorf, Dept Oncol Hematol & Bone Marrow Transplantat, Sect Pneumol, Hamburg, Germany

[5] Univ Med Ctr Hamburg Eppendorf, Microscopy Imaging Facil, Hamburg, Germany

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2024年 / 134卷 / 17期

基金：

欧洲研究理事会;

关键词：

VECTOR; LIBRARIES; VARIANTS; CELL; ENDOTHELIUM; MUTATIONS; IDES;

D O I：

10.1172/JCI174722

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页数：13

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