Optimizing the Yield of Recombinant Pharmaceutical Proteins in Plants

Abstract

The production of recombinant pharmaceutical proteins in plants is entering a new phase with the recent approval of recombinant glucocerebrosidase produced in carrot cells and the successful production of clinical-grade proteins in diverse plant-based production platforms. In the long journey from concept to product, the field of molecular farming has faced technical and economic hurdles, many reflecting the initially limited productivity of plants compared to established platforms such as mammalian cells. This challenge has been met by innovative research aiming to increase recombinant protein yields and maximize the economic benefits of plants. Research has focused on increasing the intrinsic yield capability of plants by optimizing expression construct design, and also on novel strategies to avoid epigenetic silencing and environmental effects on protein accumulation. In this article, we discuss the diverse approaches that have been used to increase the productivity of plant-based platforms for the production of recombinant pharmaceutical proteins and consider future opportunities to maximize the potential of plants and increase their competitiveness outside niche markets.

Cis-regulatory elements used to control gene expression in plants

“…This knowledge is required to strictly plan research concerning expression levels and specificity. Preliminarily experimental construction of different expression cassette combinations is highly recommended until the composition is optimized to guarantee best results (Mehrotra et al 2011;Liu et al 2013;Twyman et al 2013).…”

High-value products from plants: the challenges of process optimization

“…A key example is paclitaxel, which accumulates predominantly in the cell wall, requiring release by the addition of cellulases [32]. Similarly, recombinant proteins are easier to purify from plant cells if they are secreted, but higher yields (and specific forms of desirable modification) are often achieved by retaining the protein within the cell, so there is a trade-off between yield and recovery [33].…”

Plant Molecular Farming: Much More than Medicines

“…Standardized approaches have been developed to improve the expression construct and this can be combined with various forms of strain and process optimization to ensure the greatest synergy between the host and its environment (24,25). Strain optimization strategies are platform-specific.…”