Seed‐based expression systems for plant molecular farming
- 9 May 2010
- journal article
- review article
- Published by Wiley in Plant Biotechnology Journal
- Vol. 8 (5), 588-606
- https://doi.org/10.1111/j.1467-7652.2010.00511.x
Abstract
The evolution of the seed system provides enormous adaptability to the gymnosperms and angiosperms, because of the properties of dormancy, nutrient storage and seedling vigour. Many of the unique properties of seeds can be exploited in molecular farming applications, particularly where it is desirable to produce large quantities of a recombinant protein. Seeds of transgenic plants have been widely used to generate a raw material for the extraction and isolation of proteins and polypeptides, which can be processed into valuable biopharmaceuticals. The factors that control high-level accumulation of recombinant proteins in seed are reviewed in the following paragraphs. These include promoters and enhancers, which regulate transcript abundance. However, it is shown that subcellular trafficking and targeting of the desired polypeptides or proteins play a crucial role in their accumulation at economically useful levels. Seeds have proven to be versatile hosts for recombinant proteins of all types, including peptides or short and long polypeptides as well as complex, noncontiguous proteins like antibodies and other immunoglobulins. The extraction and recovery of recombinant proteins from seeds is greatly assisted by their dormancy properties, because this allows for long-term stability of stored products including recombinant proteins and a decoupling of processing from the growth and harvest cycles. Furthermore, the low water content and relatively low bioload of seeds help greatly in designing cost-effective manufacturing processes for the desired active pharmaceutical ingredient. The development of cGMP processes based on seed-derived materials has only been attempted by a few groups to date, but we provide a review of the key issues and criteria based on interactions with Food and Drug Administration and European Medicines Agency. This article uses 'case studies' to highlight the utility of seeds as vehicles for pharmaceutical production including: insulin, human growth hormone, lysozyme and lactoferrin. These examples serve to illustrate the preclinical and, in one case, clinical information required to move these plant-derived molecules through the research phase and into the regulatory pathway en route to eventual approval.Keywords
This publication has 58 references indexed in Scilit:
- A Plant-Derived Recombinant Human Glucocerebrosidase Enzyme—A Preclinical and Phase I InvestigationPLOS ONE, 2009
- Eukaryotic protein production in designed storage organellesBMC Biology, 2009
- Protein Body Induction: A New Tool to Produce and Recover Recombinant Proteins in PlantsMethods in molecular biology (Clifton, N.J.), 2009
- Plant-produced idiotype vaccines for the treatment of non-Hodgkin's lymphoma: Safety and immunogenicity in a phase I clinical studyProceedings of the National Academy of Sciences, 2008
- Rice-based mucosal vaccine as a global strategy for cold-chain- and needle-free vaccinationProceedings of the National Academy of Sciences, 2007
- Aberrant localization and underglycosylation of highly accumulating single-chain Fv-Fc antibodies in transgenicArabidopsisseedsProceedings of the National Academy of Sciences of the United States of America, 2007
- Extraction of Recombinant Dog Gastric Lipase from Transgenic Corn SeedJournal of Agricultural and Food Chemistry, 2006
- Molecular farming for new drugs and vaccinesEMBO Reports, 2005
- Long‐living lotus: germination and soil γ‐irradiation of centuries‐old fruits, and cultivation, growth, and phenotypic abnormalities of offspringAmerican Journal of Botany, 2002
- A trout growth hormone is expressed, correctly folded and partially glycosylated in the leaves but not the seeds of transgenic plantsTransgenic Research, 1994