Recombinant adeno-associated virus with anti-tumor necrosis factor-alpha in an experimental autoimmune uveitis model

被引：0

作者：

Li, Baiyi ^{[1
,2
]}

Zhao, Chuan ^{[1
,2
]}

Guo, Shengjie ^{[3
]}

Li, Xueru ^{[1
,2
]}

Zhang, Hui ^{[1
,2
]}

Duan, Yanan ^{[1
,2
]}

Zhang, Mi ^{[1
,2
]}

Tao, Qingqin ^{[1
,2
]}

Zhou, Peiran ^{[1
,2
]}

Li, Xiaorong ^{[1
,2
]}

Zhang, Xiaomin ^{[1
,2
]}

机构：

[1] Tianjin Med Univ, Eye Inst, Natl Clin Res Ctr Ocular Dis, Tianjin Branch,Eye Hosp,Tianjin Key Lab Retinal Fu, Tianjin, Peoples R China

[2] Tianjin Med Univ, Eye Hosp, Sch Optometry, Tianjin, Peoples R China

[3] Gritgen Therapeut Co Ltd, Suzhou, Peoples R China

来源：

EXPERIMENTAL EYE RESEARCH | 2025年 / 253卷

基金：

中国国家自然科学基金;

关键词：

GENE-THERAPY; OPEN-LABEL; AAV; ADALIMUMAB; ACTIVATION; INJECTION; EFFICACY; SAFETY;

D O I：

10.1016/j.exer.2025.110273

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

Uveitis treatment is associated with side effects and inconsistent outcomes. Existing treatments often fail to provide targeted and sustained relief; thus, novel therapeutic approaches are needed. Among these, gene therapy using adeno-associated virus (AAV) vectors target specific retinal cells, show low immunogenicity, and demonstrate sustained gene expression, making it a potential advancement in uveitis treatment. Therefore, we utilized a AAV2 system encapsulating encoded anti-tumor necrosis factor-alpha (TNF-alpha) antibody to assess its efficacy in the treatment of experimental autoimmune uveitis (EAU) in mice. Compared with the AAV2-GFP group, AAV2-ADA-injected mice showed significantly reduced clinical, OCT, and histopathological scores in EAU with lower percentages of Th1 and Th17 cells in the eyes and higher percentages of Treg cells in the draining lymph nodes (LN). This study demonstrated the safety and effects of AAV2-ADA in EAU treatment, providing a promising therapeutic strategy for uveitis.

引用

页数：10

共 49 条

[1] Systemic immunosuppressive therapies for uveitis in developing countries [J].

Agrawal, Hitesh ;

Doan, Hien ;

Pham, Brandon ;

Khosla, Amit ;

Babu, Manohar ;

McCluskey, Peter ;

Nguyen, Quan Dong ;

Sangwan, Virender ;

Reddy, Subhakar ;

Sawhney, Sujata ;

Tyagi, Mudit .

INDIAN JOURNAL OF OPHTHALMOLOGY, 2020, 68 (09) :1852-1862

[2] Intravitreal Adalimumab for Refractory Uveitis-Related Macular Edema [J].

Androudi, Sofia ;

Tsironi, Evangelia ;

Kalogeropoulos, Christos ;

Theodoridou, Athina ;

Brazitikos, Periklis .

OPHTHALMOLOGY, 2010, 117 (08) :1612-1616

[3] Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings [J].

Au, Hau Kiu Edna ;

Isalan, Mark ;

Mielcarek, Michal .

FRONTIERS IN MEDICINE, 2022, 8

[4] Medical Management of Uveitis - Current Trends [J].

Babu, Kalpana ;

Mahendradas, Padmamalini .

INDIAN JOURNAL OF OPHTHALMOLOGY, 2013, 61 (06) :277-283

[5] Long-Term Effect of Gene Therapy on Leber's Congenital Amaurosis [J].

Bainbridge, J. W. B. ;

Mehat, M. S. ;

Sundaram, V. ;

Robbie, S. J. ;

Barker, S. E. ;

Ripamonti, C. ;

Georgiadis, A. ;

Mowat, F. M. ;

Beattie, S. G. ;

Gardner, P. J. ;

Feathers, K. L. ;

Luong, V. A. ;

Yzer, S. ;

Balaggan, K. ;

Viswanathan, A. ;

de Ravel, T. J. L. ;

Casteels, I. ;

Holder, G. E. ;

Tyler, N. ;

Fitzke, F. W. ;

Weleber, R. G. ;

Nardini, M. ;

Moore, A. T. ;

Thompson, D. A. ;

Petersen-Jones, S. M. ;

Michaelides, M. ;

van den Born, L. I. ;

Stockman, A. ;

Smith, A. J. ;

Rubin, G. ;

Ali, R. R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (20) :1887-1897

[6] Pharmacotherapy for uveitis: current management and emerging therapy [J].

Barry, Robert J. ;

Quan Dong Nguyen ;

Lee, Richard W. ;

Murray, Philip I. ;

Denniston, Alastair K. .

CLINICAL OPHTHALMOLOGY, 2014, 8 :1891-1911

[7] Immune responses to retinal gene therapy using adeno-associated viral vectors-Implications for treatment success and safety [J].

Bucher, Kirsten ;

Rodriguez-Bocanegra, Eduardo ;

Dauletbekov, Daniyar ;

Fischer, M. Dominik .

PROGRESS IN RETINAL AND EYE RESEARCH, 2021, 83

[8] Viral vector platforms within the gene therapy landscape [J].

Bulcha, Jote T. ;

Wang, Yi ;

Ma, Hong ;

Tai, Phillip W. L. ;

Gao, Guangping .

SIGNAL TRANSDUCTION AND TARGETED THERAPY, 2021, 6 (01)

[9]

Caspi R.R., 2003, Curr Protoc Immunol, DOI [10.1002/0471142735.im1506-53, DOI 10.1002/0471142735.IM1506-53]

[10] Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR [J].

Cehajic-Kapetanovic, Jasmina ;

Xue, Kanmin ;

Martinez-Fernandez de la Camara, Cristina ;

Nanda, Anika ;

Davies, Alexandra ;

Wood, Laura J. ;

Salvetti, Anna Paola ;

Fischer, M. Dominik ;

Aylward, James W. ;

Barnard, Alun R. ;

Jolly, Jasleen K. ;

Luo, Edmond ;

Lujan, Brandon J. ;

Ong, Tuyen ;

Girach, Aniz ;

Black, Graeme C. M. ;

Gregori, Ninel Z. ;

Davis, Janet L. ;

Rosa, Potyra R. ;

Lotery, Andrew J. ;

Lam, Byron L. ;

Stanga, Paulo E. ;

MacLaren, Robert E. .

NATURE MEDICINE, 2020, 26 (03) :354-+

← 1 2 3 4 5 →