The impact of proline isomerization on antigen binding and the analytical profile of a trispecific anti-HIV antibody.

Proline conformational isomerization is a mechanism that affects different types of protein functions and behaviors. Using analytical characterization, structural analysis, and molecular dynamics simulations, we studied the causes of an aberrant two-peak size-exclusion chromatography profile observed for a trispecific anti-HIV antibody. We found that proline isomerization in the tyrosine-proline-proline (YPP) motif in the heavy chain complementarity-determining region (CDR)3 domain of one of the antibody arms (10e8v4) was a component of this profile.

Production of recombinant proteins in suspension-cultured plant cells.

Plants have emerged in the past decade as a suitable alternative to the current production systems for recombinant pharmaceutical proteins and, today their potential for low-cost production of high quality, much safer and biologically active mammalian proteins is largely documented. Among various plant expression systems being explored, genetically modified suspension-cultured plant cells offer a promising system for production of biopharmaceuticals. Indeed, when compared to other plant-based production platforms that have been explored, suspension-cultured plant cells have the advantage of being totally devoid of problems associated with the vagaries of weather, pest, soil and gene flow in the environment.

From Neanderthal to nanobiotech: from plant potions to pharming with plant factories.

Plants were the main source for human drugs until the beginning of the nineteenth century when plant-derived pharmaceuticals were partly supplanted by drugs produced by the industrial methods of chemical synthesis. During the last decades of the twentieth century, genetic engineering has offered an alternative to chemical synthesis, using bacteria, yeasts and animal cells as factories for the production of therapeutic proteins. After a temporary decrease in interest, plants are rapidly moving back into human pharmacopoeia, with the recent development of plant-based recombinant protein production systems offering a safe and extremely cost-effective alternative to microbial and mammalian cell cultures.

Down-regulated expression of plant-specific glycoepitopes in alfalfa.

Compared with other plant expression systems used for pharmaceutical protein production, alfalfa offers the advantage of very homogeneous N-glycosylation. Therefore, this plant was selected for further attempts at glycoengineering. Two main approaches were developed in order to humanize N-glycosylation in alfalfa.

Pharming and transgenic plants.

Plant represented the essence of pharmacopoeia until the beginning of the 19th century when plant-derived pharmaceuticals were partly supplanted by drugs produced by the industrial methods of chemical synthesis. In the last decades, genetic engineering has offered an alternative to chemical synthesis, using bacteria, yeasts and animal cells as factories for the production of therapeutic proteins. More recently, molecular farming has rapidly pushed towards plants among the major players in recombinant protein production systems.

Production and glycosylation of plant-made pharmaceuticals: the antibodies as a challenge.

Antibodies have long been recognized for their diagnostic and therapeutic potential. The rapidly increasing number of monoclonal antibodies approved for immunotherapy has paved the way to an even greater demand for these molecules. In order to satisfy this growing demand and to increase the production capacity, alternative systems based on antibody production in transgenic organisms are being actively explored.