Open AccessCosecretion of Protease Inhibitor Stabilizes Antibodies Produced by Plant Roots
Author(s) -
Slavko Komarnytsky,
Nikolai Borisjuk,
Nir Yakoby,
Alison Garvey,
Ilya Raskin
Publication year - 2006
Publication title -
plant physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.554
H-Index - 312
eISSN - 1532-2548
pISSN - 0032-0889
DOI - 10.1104/pp.105.074419
Subject(s) - antibody , monoclonal antibody , protease , secretion , calreticulin , biology , protease inhibitor (pharmacology) , immunoglobulin light chain , biochemistry , immunoglobulin g , signal peptide , microbiology and biotechnology , chemistry , peptide sequence , enzyme , immunology , endoplasmic reticulum , virus , gene , antiretroviral therapy , viral load
A plant-based system for continuous production of monoclonal antibodies based on the secretion of immunoglobulin complexes from plant roots into a hydroponic medium (rhizosecretion) was engineered to produce high levels of single-chain and full-size immunoglobulins. Replacing the original signal peptides of monoclonal antibodies with a plant-derived calreticulin signal increased the levels of antibody yield 2-fold. Cosecretion of Bowman-Birk Ser protease inhibitor reduced degradation of the immunoglobulin complexes in the default secretion pathway and further increased antibody production to 36.4 microg/g root dry weight per day for single-chain IgG1 and 21.8 microg/g root dry weight per day for full-size IgG4 antibodies. These results suggest that constitutive cosecretion of a protease inhibitor combined with the use of the plant signal peptide and the antibiotic marker-free transformation system offers a novel strategy to achieve high yields of complex therapeutic proteins secreted from plant roots.