Characterization of Recombinant Adeno-Associated Viral Transduction and Safety Profiles in Cardiomyocytes

被引：6

作者：

Ai, Jianzhong ^{[1
]}

He, Yong ^{[2
]}

Zheng, Mingxia ^{[2
]}

Wen, Yi ^{[2
]}

Zhang, Huan ^{[2
]}

Huang, Fangyang ^{[2
]}

Zhu, Ye ^{[2
]}

机构：

[1] Sichuan Univ, West China Hosp, Dept Urol, Inst Urol, Chengdu, Sichuan, Peoples R China

[2] Sichuan Univ, West China Hosp, Dept Cardiol, Guoxue Xiang 37, Chengdu 610041, Sichuan, Peoples R China

来源：

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY | 2018年 / 48卷 / 05期

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

Adeno-associated virus; Safety profile; Gene therapy; Heart diseases; Transduction efficacy; GENE-THERAPY; RENEWAL;

D O I：

10.1159/000492510

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Background/Aims: Cardiovascular diseases (CVD) are the leading causes for human mortality. However, the effective treatment for these diseases are still lacking. Currently, gene therapy could be a potential way for efficiently treating heart diseases. The aim of our study is to analyze the transduction efficacy and safety profile of recombinant adeno associated virus (AAV) serotype 9 for cardiomyocytes in vivo and in vitro. Methods: We produced rAAV serotype 9 expressing enhanced green fluorescence protein (EGFP) driven by a cardiac troponin T (cTNT) promoter, and characterized its transduction efficiency in primary cultured cardiomyocytes in vitro, and in wild-type mouse heart tissue in vivo. Results: Our data showed that rAAV9 efficiently transduced mouse cardiomyocytes in vitro. Following intravenous injection, rAAV9 could efficiently and safely transduce cardiomyocytes that are involved in heart diseases. Conclusion: Our findings suggested that rAAV9 can efficiently and safely transduce cardiomyocytes in vitro and/or in vivo. The rAAV9 serotype vector could constitute a powerful toolbox for future gene therapy of heart diseases. (C) 2018 The Author(s) Published by S. Karger AG, Basel

引用

页码：1894 / 1900

页数：7

共 50 条

[21] Gene therapy for Parkinson's disease using recombinant adeno-associated viral vectors [J].

Muramatsu, S ;

Tsukada, H ;

Nakano, I ;

Ozawa, K .

EXPERT OPINION ON BIOLOGICAL THERAPY, 2005, 5 (05) :663-671

[22] Analytical Ultracentrifugation as an Approach to Characterize Recombinant Adeno-Associated Viral Vectors [J].

Burnham, Brenda ;

Nass, Shelley ;

Kong, Elton ;

Mattingly, MaryEllen ;

Woodcock, Denise ;

Song, Antonius ;

Wadsworth, Samuel ;

Cheng, Seng H. ;

Scaria, Abraham ;

O'Riordan, Catherine R. .

HUMAN GENE THERAPY METHODS, 2015, 26 (06) :228-242

[23] Production and purification of serotype 1, 2, and 5 recombinant adeno-associated viral vectors [J].

Zolotukhin, S ;

Potter, M ;

Zolotukhin, I ;

Sakai, Y ;

Loiler, S ;

Fraites, TJ ;

Chiodo, VA ;

Phillipsberg, T ;

Muzyczka, N ;

Hauswirth, WW ;

Flotte, TR ;

Byrne, BJ ;

Snyder, RO .

METHODS, 2002, 28 (02) :158-167

[24] Manufacturing of recombinant adeno-associated viral vectors: new technologies are welcome [J].

Ayuso, Eduard .

MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT, 2016, 3 :15049

[25] Vascular-targeted recombinant adeno-associated viral vectors for the treatment of rare diseases [J].

Koerbelin, Jakob ;

Schwaninger, Markus ;

Trepel, Martin .

RARE DISEASES, 2016, 4 (01)

[26] Adeno-Associated Viral Vectors in the Treatment of Epilepsy [J].

Mullagulova, Aysilu I. ;

Timechko, Elena E. ;

Solovyeva, Valeriya V. ;

Yakimov, Alexey M. ;

Ibrahim, Ahmad ;

Dmitrenko, Diana D. ;

Sufianov, Albert A. ;

Sufianova, Galina Z. ;

Rizvanov, Albert A. .

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2024, 25 (22)

[27] Engraftment of a Galactose Receptor Footprint onto Adeno-associated Viral Capsids Improves Transduction Efficiency [J].

Shen, Shen ;

Horowitz, Eric D. ;

Troupes, Andrew N. ;

Brown, Sarah M. ;

Pulicherla, Nagesh ;

Samulski, Richard J. ;

Agbandje-McKenna, Mavis ;

Asokan, Aravind .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (40) :28814-28823

[28] Adeno-associated viral vector integration: implications for long-term efficacy and safety [J].

Batty, Paul ;

Lillicrap, David .

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2024, 22 (11) :2945-2960

[29] Advances in Recombinant Adeno-Associated Viral Vectors for Gene Delivery [J].

Petrs-Silva, Hilda ;

Linden, Rafael .

CURRENT GENE THERAPY, 2013, 13 (05) :335-345

[30] Inhibition of recombinant adeno-associated virus (rAAV) transduction by bronchial secretions from cystic fibrosis patients [J].

Virella-Lowell, I ;

Poirier, A ;

Chesnut, KA ;

Brantly, M ;

Flotte, TR .

GENE THERAPY, 2000, 7 (20) :1783-1789

← 1 2 3 4 5 →