DESIGN, INTRACELLULAR EXPRESSION, AND ACTIVITY OF A HUMAN ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP120 SINGLE-CHAIN ANTIBODY

被引:231
作者
MARASCO, WA [1 ]
HASELTINE, WA [1 ]
CHEN, SY [1 ]
机构
[1] HARVARD UNIV,SCH MED,SCH PUBL HLTH,DANA FARBER CANC INST,DEPT PATHOL,DIV HUMAN RETROVIROL,BOSTON,MA 02115
关键词
HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 ENVELOPE PROTEIN; INTRACELLULAR ANTIBODY; AIDS; CD4+ T-CELLS; GENE THERAPY;
D O I
10.1073/pnas.90.16.7889
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:7889 / 7893
页数:5
相关论文
共 36 条
[1]   MAJOR GLYCOPROTEIN ANTIGENS THAT INDUCE ANTIBODIES IN AIDS PATIENTS ARE ENCODED BY HTLV-III [J].
ALLAN, JS ;
COLIGAN, JE ;
BARIN, F ;
MCLANE, MF ;
SODROSKI, JG ;
ROSEN, CA ;
HASELTINE, WA ;
LEE, TH ;
ESSEX, M .
SCIENCE, 1985, 228 (4703) :1091-1094
[2]   EXPRESSION AND TARGETING OF INTRACELLULAR ANTIBODIES IN MAMMALIAN-CELLS [J].
BIOCCA, S ;
NEUBERGER, MS ;
CATTANEO, A .
EMBO JOURNAL, 1990, 9 (01) :101-108
[3]   SINGLE-CHAIN ANTIGEN-BINDING PROTEINS [J].
BIRD, RE ;
HARDMAN, KD ;
JACOBSON, JW ;
JOHNSON, S ;
KAUFMAN, BM ;
LEE, SM ;
LEE, T ;
POPE, SH ;
RIORDAN, GS ;
WHITLOW, M .
SCIENCE, 1988, 242 (4877) :423-426
[4]   POSTTRANSLATIONAL ASSOCIATION OF IMMUNOGLOBULIN HEAVY-CHAIN BINDING-PROTEIN WITH NASCENT HEAVY-CHAINS IN NONSECRETING AND SECRETING HYBRIDOMAS [J].
BOLE, DG ;
HENDERSHOT, LM ;
KEARNEY, JF .
JOURNAL OF CELL BIOLOGY, 1986, 102 (05) :1558-1566
[5]   PREVENTION OF HIV-1 GLYCOPROTEIN TRANSPORT BY SOLUBLE CD4 RETAINED IN THE ENDOPLASMIC-RETICULUM [J].
BUONOCORE, L ;
ROSE, JK .
NATURE, 1990, 345 (6276) :625-628
[6]   OLIGOMERIZATION, TRANSPORT, AND GOLGI RETENTION OF PUNTA-TORO VIRUS GLYCOPROTEINS [J].
CHEN, SY ;
COMPANS, RW .
JOURNAL OF VIROLOGY, 1991, 65 (11) :5902-5909
[7]   MAKING ANTIBODY FRAGMENTS USING PHAGE DISPLAY LIBRARIES [J].
CLACKSON, T ;
HOOGENBOOM, HR ;
GRIFFITHS, AD ;
WINTER, G .
NATURE, 1991, 352 (6336) :624-628
[8]   CD4 IS RETAINED IN THE ENDOPLASMIC-RETICULUM BY THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GLYCOPROTEIN PRECURSOR [J].
CRISE, B ;
BUONOCORE, L ;
ROSE, JK .
JOURNAL OF VIROLOGY, 1990, 64 (11) :5585-5593
[9]   THE CD4 (T4) ANTIGEN IS AN ESSENTIAL COMPONENT OF THE RECEPTOR FOR THE AIDS RETROVIRUS [J].
DALGLEISH, AG ;
BEVERLEY, PCL ;
CLAPHAM, PR ;
CRAWFORD, DH ;
GREAVES, MF ;
WEISS, RA .
NATURE, 1984, 312 (5996) :763-767
[10]   A SINGLE AMINO-ACID SUBSTITUTION IN THE VARIABLE REGION OF THE LIGHT CHAIN SPECIFICALLY BLOCKS IMMUNOGLOBULIN SECRETION [J].
DUL, JL ;
ARGON, Y .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (20) :8135-8139