Marasco W A, Haseltine W A, Chen S Y
Department of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7889-93. doi: 10.1073/pnas.90.16.7889.
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 interchain 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.
一种源自人单克隆抗体的单链抗体已被设计用于在真核细胞中进行细胞内表达，该人单克隆抗体可识别1型人类免疫缺陷病毒（HIV-1）包膜蛋白的CD4结合区域。该单链抗体由免疫球蛋白重链前导序列以及通过链间连接子连接的重链和轻链可变区组成。该抗体在细胞内质网中稳定表达并保留，对细胞无毒。该抗体在细胞内与包膜蛋白结合，并抑制包膜前体的加工和多核体形成。表达该单链抗体的细胞产生的HIV-1颗粒的感染性大幅降低。这些研究说明了设计能在细胞内结合并使分子失活的抗体的可行性。作用于细胞内靶分子的抗体应为研究以及控制传染病和其他疾病提供有用的工具。
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