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

共 50 条

[11] Characterization of Gene Therapy Associated Uveitis Following Intravitreal Adeno-Associated Virus Injection in Mice [J].

Tummala, Gayathri ;

Crain, Adam ;

Rowlan, Jessica ;

Pepple, Kathryn L. .

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2021, 62 (02)

[12] Ocular Gene Therapy: An Evaluation of Recombinant Adeno-Associated Virus-Mediated Gene Therapy Interventions for the Treatment of Ocular Disease [J].

Roy, Kamolika ;

Stein, Linda ;

Kaushal, Shalesh .

HUMAN GENE THERAPY, 2010, 21 (08) :915-927

[13] Recombinant adeno-associated virus vectors for cystic fibrosis gene therapy [J].

Flotte, TR .

CURRENT OPINION IN MOLECULAR THERAPEUTICS, 2001, 3 (05) :497-502

[14] Adeno-associated virus serotypes: Vector toolkit for human gene therapy [J].

Wu, Zhijian ;

Asokan, Aravind ;

Samulski, R. Jude .

MOLECULAR THERAPY, 2006, 14 (03) :316-327

[15] Adeno-associated virus vector-mediated gene delivery to the vasculature and kidney [J].

Kapturczak, MH ;

Chen, SF ;

Agarwal, A .

ACTA BIOCHIMICA POLONICA, 2005, 52 (02) :293-299

[16] Neutralizing Antibodies Against Adeno-associated Viruses in Inflammatory Bowel Disease Patients: Implications for Gene Therapy [J].

van der Marel, Sander ;

Comijn, Elisabeth M. ;

Verspaget, Hein W. ;

van Deventer, Sander ;

van den Brink, Gijs R. ;

Petry, Harald ;

Hommes, Daniel W. ;

Ferreira, Valerie .

INFLAMMATORY BOWEL DISEASES, 2011, 17 (12) :2436-2442

[17] Intraparenchymal delivery of adeno-associated virus vectors for the gene therapy of neurological diseases [J].

Kumagai, Shinichi ;

Nakajima, Takeshi ;

Muramatsu, Shin-ichi .

EXPERT OPINION ON BIOLOGICAL THERAPY, 2024, 24 (08) :773-785

[18] Next-generation strategies to improve safety and efficacy of adeno-associated virus-based gene therapy for hemophilia: lessons from clinical trials in other gene therapies [J].

Di Minno, Giovanni ;

Miesbach, Wolfgang ;

Castaman, Giancarlo ;

Peyvandi, Flora .

HAEMATOLOGICA, 2024, 109 (12) :3879-3891

[19] Considerations for Preclinical Safety Assessment of Adeno-Associated Virus Gene Therapy Products [J].

Assaf, Basel T. ;

Whiteley, Laurence O. .

TOXICOLOGIC PATHOLOGY, 2018, 46 (08) :1020-1027

[20] In Search of Adeno-Associated Virus Vectors With Enhanced Cardiac Tropism for Gene Therapy [J].

Sasaki, Natsuki ;

Kok, Cindy Y. ;

Westhaus, Adrian ;

Alexander, Ian E. ;

Lisowski, Leszek ;

Kizana, Eddy .

HEART LUNG AND CIRCULATION, 2023, 32 (07) :816-824

← 1 2 3 4 5 →