REVIEW The use of plants for the production of therapeutic human peptides Chiara Lico • Luca Santi • Richard M. Twyman • Mario Pezzotti • Linda Avesani Received: 31 October 2011 / Revised: 13 December 2011 / Accepted: 13 December 2011 / Published online: 5 January 2012 Ó Springer-Verlag 2012 Abstract Peptides have unique properties that make them useful drug candidates for diverse indications, including allergy, infectious disease and cancer. Some peptides are intrinsically bioactive, while others can be used to induce precise immune responses by defining a minimal immu- nogenic region. The limitations of peptides, such as met- abolic instability, short half-life and low immunogenicity, can be addressed by strategies such as multimerization or fusion to carriers, to improve their pharmacological prop- erties. The remaining major drawback is the cost of pro- duction using conventional chemical synthesis, which is also difficult to scale-up. Over the last 15 years, plants have been shown to produce bioactive and immunogenic peptides economically and with the potential for large- scale synthesis. The production of peptides in plants is usually achieved by the genetic fusion of the corresponding nucleotide sequence to that of a carrier protein, followed by stable nuclear or plastid transformation or transient expression using bacterial or viral vectors. Chimeric plant viruses or virus-like particles can also be used to display peptide antigens, allowing the production of polyvalent vaccine candidates. Here we review progress in the field of plant-derived peptides over the last 5 years, addressing new challenges for diverse pathologies. Keywords Therapeutic peptide Á Molecular pharming Á Transgenic plants Á Chimeric plant virus Á Plant-derived vaccine Introduction Peptides play an important role as mediators of key bio- logical functions, and their unique properties, in terms of efficacy, selectivity, specificity and low toxicity, make them particularly attractive as therapeutic, prophylactic and diagnostic reagents for diverse indications such as allergy, cardiovascular disease, infectious diseases, immunological disorders, gastrointestinal dysfunction and cancer and imaging. The distinction between peptide and protein therapeutics can be ambiguous, since any polymer of two or more amino acids linked by peptide bonds is considered a peptide but the minimum number of amino acid residues required to form a protein is arbitrary. Here, we define the cutoff value as 100, so that any chain of fewer than 100 amino acids is considered a peptide and not a protein, as suggested by Lien and Lowman (2003). Peptides were initially considered poor drug candidates because of their inability to cross biological membranes and cellular barriers efficiently, and in some cases also their low Communicated by R. Reski. A contribution to the Special Issue: Plant Molecular Pharming in 2012 and Beyond. C. Lico Laboratorio di Biotecnologie, Unita ` Tecnica BIORAD, ENEA C.R. Casaccia, 00123 Rome, Italy L. Santi Department of Agriculture, Forests, Nature and Energy (D.A.F.N.E.), University of Tuscia, Via San Camillo de Lelliss, 01100 Viterbo, Italy R. M. Twyman Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK M. Pezzotti Á L. Avesani (&) Dipartimento di Biotecnologie, Universita ` degli Studi di Verona, Strada Le Grazie, 15, 37134 Verona, Italy e-mail: linda.avesani@univr.it 123 Plant Cell Rep (2012) 31:439–451 DOI 10.1007/s00299-011-1215-7