DESIGN, INTRACELLULAR EXPRESSION, AND ACTIVITY OF A HUMAN ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP120 SINGLE-CHAIN ANTIBODY
DESIGN, INTRACELLULAR EXPRESSION, AND ACTIVITY OF A HUMAN ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP120 SINGLE-CHAIN ANTIBODY
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DOI：
10.1073/pnas.90.16.7889
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发表时间：
1993-08-15
影响因子：
11.1
通讯作者：
CHEN, SY
中科院分区：
文献类型：
--
作者：
MARASCO, WA;HASELTINE, WA;CHEN, SY
已设计了一种单链抗体用于真核细胞中的细胞内表达，该单链抗体来源于识别人类免疫缺陷病毒1型（HIV-1）包膜蛋白的CD 4结合区的人单克隆抗体。单链抗体由免疫球蛋白重链前导序列和通过链间接头连接的重链和轻链可变区组成。该抗体稳定表达并保留在内质网中，对细胞无毒。抗体结合细胞内的包膜蛋白，并抑制包膜前体的加工和合胞体形成。由表达单链抗体的细胞产生的HIV-1颗粒的感染性大大降低。这些研究说明了设计细胞内结合和抑制分子的抗体的可行性。作用于细胞内靶分子的抗体应该为研究以及控制传染病和其他疾病提供有用的工具。
A single-chain antibody, derived from a human monoclonal antibody that recognizes the CD4 binding region of the human immunodeficiency virus type 1 (HIV-1) envelope protein, has been designed for intracellular expression in eukaryotic cells. The single-chain antibody is composed of an immunoglobulin heavy-chain leader sequence and heavy- and light-chain variable regions that are joined by an inter-chain linker. The antibody is stably expressed and retained in the endoplasmic reticulum and is not toxic to the cells. The antibody binds to the envelope protein within the cell and inhibits processing of the envelope precursor and syncytia formation. The infectivity of the HIV-1 particles produced by cells that express the single-chain antibody is substantially reduced. These studies illustrate the feasibility of designing antibodies that bind and inactivate molecules intracellularly. Antibodies that act on target molecules within cells should provide a useful tool for research as well as for control of infectious and other diseases.