Subcellular Accumulation and Modification of Pharmaceutical Proteins in Different Plant Tissues

Abstract

Many plant species and tissues have been investigated as production and delivery vehicles for recombinant pharmaceutical proteins. Examples include cultured cells, whole aquatic plants and transgenic plants expressing recombinant proteins in their leaves, seeds, fruits or tubers/roots. Each platform has unique properties in terms of production time, environmental containment, scalability and overall costs. Plant tissues also differ in their abilities to sort, modify and accumulate proteins. Seeds are naturally adapted for protein accumulation and possess specialized storage organelles that may be exploited to accumulate recombinant proteins, offering stability both in planta and after harvest. Generally, the post-harvest stabilizing effect offered by storage tissues is advantageous for pharmaceuticals, allowing them to be delivered via the mucosal route because they are better able to withstand the harsh microenvironment when protected by the plant matrix. Native storage organelles such as starch granules, protein storage vacuoles and protein bodies thus offer interesting possibilities for the delivery of vaccines and antibodies, as well as novel storage organelles that can be induced ectopically in non-storage tissues. The specialization and distinct intracellular organization of storage tissues also affect the trafficking and modification of recombinant proteins. The N-glycosylation of recombinant glycoproteins often differs subtly depending on the plant species and tissue, reflecting both the availability of different sets of glycan-modifying enzymes and the compartmentalization of the proteins. Where a specific glycan structure is required, it is therefore important to choose the appropriate plant system as a production platform.