利用MDV载体递呈靶向ALV-J的CRISPR/Cas9系统预防MDV和ALV-J感染的研究

J亚群禽白血病病毒（ALV-J）和鸡马立克氏病病毒（MDV）是两种重要的禽免疫抑制性和致瘤性病毒。ALV-J近几年发病日趋严重，已经影响到我国养鸡业的发展，但当前对该病仍没有有效的疫苗和治疗措施。ALV-J与MDV的混合感染进一步增加了防控的难度。CRISPR/Cas9是近年来出现的一种全新的基因编辑技术，在病毒性疾病的治疗中具有重大的潜在应用价值。本项目首先构建靶向ALV-J的CRISPR/Cas9系统，研究其在体外阻止ALV-J感染宿主细胞的作用以及清除ALV-J转化细胞系中前病毒DNA的作用；在此基础上，以MDV为载体递呈靶向ALV-J的CRISPR/Cas9系统，构建重组病毒疫苗株，检测其对ALV-J的清除作用和对MDV的预防效果。本项目应用MDV载体递呈靶向ALV-J的CRISPR/Cas9系统，探索其对ALV-J和MDV感染的预防作用，从而为两病的防控提供一种新的方法。

Avian leukosis virus subgroup J (ALV-J) and Marek’s disease virus (MDV) are two important immunosuppressive and oncogenic viruses infecting chickens. The pathogenicity of ALV-J is more and more severer these years, affecting the development of the poultry industry in our country. However, no effective vaccines and treatments are currently available for ALV-J prevention. Furthermore, the co-infection of ALV-J and MDV further increased the difficulty for these diseases prevention. CRISPR/Cas9 is a novel genome-editing tool emerged in recently years, which has great potential in the treatments of viral diseases. In this project, we would firstly construct the CRSIPR/Cas9 system targeting ALV-J. Then, the effects of the CRSIPR/Cas9 system to prevent the infection of ALV-J and to disrupt the latent ALV-J provirus would be studied. Finally, the recombinant MDV expressing the CRSIPR/Cas9 targeting ALV-J would be constructed and its efficacy to prevent MDV and ALV-J infection would be detected. By delivering the ALV-J targeted CRISPR/Cas9 using MDV-vectored vaccine, this project might provide a novel strategy for MDV and ALV-J prevention.