一种非整合型慢病毒方法克服了Cas9诱导的免疫排斥反应，从而建立了一个具有免疫活性的转移性肾癌模型。
A Non-integrating Lentiviral Approach Overcomes Cas9-Induced Immune Rejection to Establish an Immunocompetent Metastatic Renal Cancer Model.
作者信息
Hu Junhui, Schokrpur Shiruyeh, Archang Maani, Hermann Kip, Sharrow Allison C, Khanna Prateek, Novak Jesse, Signoretti Sabina, Bhatt Rupal S, Knudsen Beatrice S, Xu Hua, Wu Lily
机构信息
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Department of Urology and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
出版信息
Mol Ther Methods Clin Dev. 2018 Feb 23;9:203-210. doi: 10.1016/j.omtm.2018.02.009. eCollection 2018 Jun 15.
The CRISPR-based technology has revolutionized genome editing in recent years. This technique allows for gene knockout and evaluation of function in cell lines in a manner that is far easier and more accessible than anything previously available. Unfortunately, the ability to extend these studies to syngeneic murine cell line implantation is limited by an immune response against cells transduced to stably express Cas9. In this study, we demonstrate that a non-integrating lentiviral vector approach can overcome this immune rejection and allow for the growth of transduced cells in an immunocompetent host. This technique enables the establishment of a von Hippel-Lindau () gene knockout RENCA cell line in BALB/c mice, generating an improved model of immunocompetent, metastatic renal cell carcinoma (RCC).
近年来，基于CRISPR的技术彻底改变了基因组编辑。这项技术能够以一种比以往任何方法都更容易且更可行的方式，在细胞系中实现基因敲除和功能评估。不幸的是，将这些研究扩展到同基因小鼠细胞系植入的能力受到针对稳定表达Cas9的转导细胞的免疫反应的限制。在本研究中，我们证明了一种非整合慢病毒载体方法可以克服这种免疫排斥，并使转导细胞在免疫活性宿主中生长。这项技术能够在BALB/c小鼠中建立一种冯·希佩尔-林道（VHL）基因敲除的RENCA细胞系，从而生成一种改进的免疫活性转移性肾细胞癌（RCC）模型。
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