Molecular farming of recombinant antibodies in plants

被引:99
作者
Schillberg, S
Fischer, R
Emans, N
机构
[1] Fraunhofer Inst Mol Biol & Appl Ecol, IME, Grafschaft, D-57392 Schmallenberg, Germany
[2] Rhein Westfal TH Aachen, Inst Mol Biotechnol Biol 7, D-52074 Aachen, Germany
关键词
recombinant protein; transgenic plant; antibody production; purification; biotechnology;
D O I
10.1007/s000180300037
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Antibodies represent a large proportion of therapeutic drugs currently in development. In most cases, they are produced in mammalian cell lines or transgenic animals because these have been shown to fold and assemble the proteins correctly and generate authentic glycosylation patterns. However, such expression systems are expensive, difficult to scale up and there are safety concerns due to potential contamination with pathogenic organisms or oncogenic DNA sequences. Plants represent an inexpensive, efficient and safe alternative for the production of recombinant antibodies. Research over the last 10 years has shown that plants can produce a variety of functional antibodies and there is now intense interest in scaling up production to commercial levels. In this review, we discuss the advantages of plants over traditional expression systems, describe how antibody expression in plants is achieved and optimized and then consider the practical issues concerning large-scale molecular farming in plants. The first plant-produced therapeutic antibodies are already in clinical trials, and, given the economic benefits of this production system, we are likely to see many more recombinant antibodies produced in this manner in the future.
引用
收藏
页码:433 / 445
页数:13
相关论文
共 110 条
[31]   Expression and characterization of bispecific single-chain Fv fragments produced in transgenic plants [J].
Fischer, R ;
Schumann, D ;
Zimmermann, S ;
Drossard, J ;
Sack, M ;
Schillberg, S .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1999, 262 (03) :810-816
[32]   Affinity-purification of a TMV-specific recombinant full-size antibody from a transgenic tobacco suspension culture [J].
Fischer, R ;
Liao, YC ;
Drossard, J .
JOURNAL OF IMMUNOLOGICAL METHODS, 1999, 226 (1-2) :1-10
[33]   Expression and characterization of bryodin 1 and a bryodin 1-based single-chain immunotoxin from tobacco cell culture [J].
Francisco, JA ;
Gawlak, SL ;
Miller, M ;
Bathe, J ;
Russell, D ;
Chace, D ;
Mixan, B ;
Zhao, L ;
Fell, HP ;
Siegall, CB .
BIOCONJUGATE CHEMISTRY, 1997, 8 (05) :708-713
[34]   Functional expression in bacteria and plants of an scFv antibody fragment against tospoviruses [J].
Franconi, A ;
Roggero, P ;
Pirazzi, P ;
Arias, FJ ;
Desiderio, A ;
Bitti, O ;
Pashkoulov, D ;
Mattei, B ;
Bracci, L ;
Masenga, V ;
Milne, RG ;
Benvenuto, E .
IMMUNOTECHNOLOGY, 1999, 4 (3-4) :189-201
[35]   Very high expression of an anti-carcinoembryonic antigen single chain Fv antibody fragment in the yeast Pichia pastoris [J].
Freyre, FM ;
Vázquez, JE ;
Ayala, M ;
Canaán-Haden, L ;
Bell, H ;
Rodríguez, I ;
González, A ;
Cintado, A ;
Gavilondo, JV .
JOURNAL OF BIOTECHNOLOGY, 2000, 76 (2-3) :157-163
[36]   Translation in plants - Rules and exceptions [J].
Futterer, J ;
Hohn, T .
PLANT MOLECULAR BIOLOGY, 1996, 32 (1-2) :159-189
[37]   Translational control of cellular and viral mRNAs [J].
Gallie, DR .
PLANT MOLECULAR BIOLOGY, 1996, 32 (1-2) :145-158
[38]   Transgenic plants as protein factories [J].
Giddings, G .
CURRENT OPINION IN BIOTECHNOLOGY, 2001, 12 (05) :450-454
[39]   Use of plant roots for phytoremediation and molecular farming [J].
Gleba, D ;
Borisjuk, NV ;
Borisjuk, LG ;
Kneer, R ;
Poulev, A ;
Sarzhinskaya, M ;
Dushenkov, S ;
Logendra, S ;
Gleba, YY ;
Raskin, I .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (11) :5973-5977
[40]   DIRECT EXPRESSION IN ESCHERICHIA-COLI OF A DNA-SEQUENCE CODING FOR HUMAN GROWTH-HORMONE [J].
GOEDDEL, DV ;
HEYNEKER, HL ;
HOZUMI, T ;
ARENTZEN, R ;
ITAKURA, K ;
YANSURA, DG ;
ROSS, MJ ;
MIOZZARI, G ;
CREA, R ;
SEEBURG, PH .
NATURE, 1979, 281 (5732) :544-548