Antithrombotic Effect of shRNA Target F12 Mediated by Adeno-Associated Virus

Fanfan Li; Xiao Yang; Jie Liu; Kuangyi Shu; Chenfang Shen; Tao Chen; Wei Yang; Shanshan Li; Xiaoou Wang; Minghua Jiang

doi:10.1016/j.omtn.2019.02.026

Antithrombotic Effect of shRNA Target F12 Mediated by Adeno-Associated Virus

Mol Ther Nucleic Acids. 2019 Jun 7:16:295-301. doi: 10.1016/j.omtn.2019.02.026. Epub 2019 Mar 15.

Authors

Fanfan Li¹, Xiao Yang¹, Jie Liu¹, Kuangyi Shu¹, Chenfang Shen¹, Tao Chen¹, Wei Yang¹, Shanshan Li¹, Xiaoou Wang¹, Minghua Jiang²

Affiliations

¹ The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.
² The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China. Electronic address: minghua93@126.com.

Abstract

Coagulation factor XII (FXII) plays a crucial role in thrombosis. Moreover, deficiencies in FXII are not associated with excessive bleeding, and its depletion exhibits satisfactory protective effect on thrombus formation. Several strategies targeting FXII have been applied to inhibit thrombosis formation. In this study, C57BL/6 mice were injected with adeno-associated virus (AAV) to identify the role of short hairpin RNA (shRNA) in thrombosis. Differences in liver FXII, coagulation function, and thrombus formation were detected. The potential side effects of FXII were then evaluated through analysis of tail bleeding, biochemical indices, and pathological sections. Results showed that shRNAs, especially shRNA2, carried by AAV, effectively reduced the expression of FXII. Furthermore, only shRNA2 demonstrated an anti-thrombosis effect on multiple models without hemorrhage and side effects. Hence the novel approach of AAV-based shRNA is specific and safe for inhibiting FXII and thrombosis.