中文摘要：
腺病毒作为基因治疗载体拥有巨大应用潜力，但机体预先存在的免疫应答限制了它的广泛使用。目前尚不清楚造成这一免疫阻碍的具体机制：抗体可强烈抑制转基因表达，却不会阻碍载体向靶细胞的基因递送。本文证实：体内抗体对腺病毒基因递送的阻断作用，由胞质抗体受体 TRIM21 介导。敲除 TRIM21 基因，或对抗体进行单位点突变，就足以将转基因表达恢复至接近未免疫个体的水平。
TRIM21 还会阻碍疫苗载体诱导细胞毒性 T 细胞应答，使机体无法对后续流感病毒感染以及移植肿瘤产生保护性免疫。此外，静脉注射腺病毒载体时，机体预存免疫还会引发免疫应答增强效应。对载体转导组织开展转录组分析发现，TRIM21 特异性介导数百个免疫基因上调，其中绝大多数属于固有免疫通路组分。
综上，本研究阐明了预存免疫阻碍腺病毒基因治疗的核心机制；证实 TRIM21 可在体内高效阻断基因递送，同时启动快速的免疫转录程序。
英文摘要：
Adenovirus has enormous potential as a gene-therapy vector, but preexisting immunity limits its widespread application. What is responsible for this immune block is unclear because antibodies potently inhibit transgene expression without impeding gene transfer into target cells. Here we show that antibody prevention of adenoviral gene delivery in vivo is mediated by the cytosolic antibody receptor TRIM21. Genetic KO of TRIM21 or a single-antibody point mutation is sufficient to restore transgene expression to near-naïve immune levels. TRIM21 is also responsible for blocking cytotoxic T cell induction by vaccine vectors, preventing a protective response against subsequent influenza infection and an engrafted tumor. Furthermore, adenoviral preexisting immunity can lead to an augmented immune response upon i.v. administration of the vector. Transcriptomic analysis of vector-transduced tissue reveals that TRIM21 is responsible for the specific up-regulation of hundreds of immune genes, the majority of which are components of the intrinsic or innate response. Together, these data define a major mechanism underlying the preimmune block to adenovirus gene therapy and demonstrate that TRIM21 efficiently blocks gene delivery in vivo while simultaneously inducing a rapid program of immune transcription.
论文信息：
论文题目：TRIM21 mediates antibody inhibition of adenovirus-based gene delivery and vaccination
期刊名称：PNAS
时间期卷：115 (41) 10440-10445
Doi.org/10.1073/pnas.1806314115
产品信息：
货号：CP-010-010
规格：10ml+10ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes&Control Liposomes
办事处：靶点科技
Clodronate Liposomes氯膦酸盐脂质体清除腺病毒递送小鼠肝脏巨噬细胞。荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于PNAS：TRIM21介导抗体对基于腺病毒的基因递送和疫苗接种的抑制作用。
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除巨噬细胞的材料和方法：
In vivo macrophage depletion
Liver Macrophage Depletion.
巨噬细胞清除材料和方法文献截图：
