Evaluation of unintended effects in the composition of tomatoes expressing a human immunoglobulin A against rotavirus.

The production of neutralizing immunoglobulin A (IgA) in edible fruits as a means of oral passive immunization is a promising strategy for the inexpensive treatment of mucosal diseases. This approach is based on the assumption that the edible status remains unaltered in the immunoglobulin-expressing fruit, and therefore extensive purification is not required for mucosal delivery. However, unintended effects associated with IgA expression such as toxic secondary metabolites and protein allergens cannot be dismissed a priori and need to be investigated. This paper describes a collection of independent transgenic tomato lines expressing a neutralizing human IgA against rotavirus, a mucosal pathogen producing severe diarrhea episodes. This collection was used to evaluate possible unintended effects associated with recombinant IgA expression. A comparative analysis of protein and secondary metabolite profiles using wild type lines and other commercial varieties failed to find unsafe features significantly associated with IgA expression. Preliminary, the data indicate that formulations derived from IgA tomatoes are as safe for consumption as equivalent formulations derived from wild type tomatoes.

[1]  Martin Giersberg,et al.  Antibody expressing pea seeds as fodder for prevention of gastrointestinal parasitic infections in chickens , 2009, BMC biotechnology.

[2]  D. Ohta,et al.  Metabolic profiling of transgenic potato tubers expressing Arabidopsis dehydration response element-binding protein 1A (DREB1A). , 2013, Journal of agricultural and food chemistry.

[3]  J. G. Roddick,et al.  Biosynthesis and degradation of α-tomatine in developing tomato fruits , 1985 .

[4]  M. Taylor,et al.  Assessing the potential for unintended effects in genetically modified potatoes perturbed in metabolic and developmental processes. Targeted analysis of key nutrients and anti-nutrients , 2006, Transgenic Research.

[5]  J. Keurentjes,et al.  Untargeted large-scale plant metabolomics using liquid chromatography coupled to mass spectrometry , 2007, Nature Protocols.

[6]  Mauro Fasano,et al.  Proteomics as a tool to improve investigation of substantial equivalence in genetically modified organisms: The case of a virus‐resistant tomato , 2004, Proteomics.

[7]  Diego Orzaez,et al.  Neutralizing antibodies against rotavirus produced in transgenically labelled purple tomatoes. , 2012, Plant biotechnology journal.

[8]  Antonio Granell,et al.  Manufacturing antibodies in the plant cell , 2009, Biotechnology journal.

[9]  L. Hothorn,et al.  Statistical analysis used in the nutritional assessment of novel food using the proof of safety. , 2006, Regulatory toxicology and pharmacology : RTP.

[10]  C. Goulet,et al.  Tubers from potato lines expressing a tomato Kunitz protease inhibitor are substantially equivalent to parental and transgenic controls. , 2010, Plant biotechnology journal.

[11]  J. G. Roddick,et al.  Changes in the Alkaloid Content of Developing Fruits of Tomato (Lycopersicon esculentum Mill.)I. ANALYSES OF CULTIVARS AND MUTANTS WITH DIFFERENT RIPENING CHARACTERISTICS , 1984 .

[12]  I. Sola,et al.  An antibody derivative expressed from viral vectors passively immunizes pigs against transmissible gastroenteritis virus infection when supplied orally in crude plant extracts , 2006, Plant biotechnology journal.

[13]  M. Friedman,et al.  .alpha.-Tomatine Content in Tomato and Tomato Products Determined by HPLC with Pulsed Amperometric Detection , 1995 .

[14]  Sam Millet,et al.  Orally fed seeds producing designer IgAs protect weaned piglets against enterotoxigenic Escherichia coli infection , 2013, Proceedings of the National Academy of Sciences.

[15]  R. Fischer,et al.  An Antisense Gene Stimulates Ethylene Hormone Production during Tomato Fruit Ripening. , 1992, The Plant cell.

[16]  A. Scaloni,et al.  Leaf proteome analysis of transgenic plants expressing antiviral antibodies. , 2009, Journal of proteome research.

[17]  Kazuki Saito,et al.  Covering Chemical Diversity of Genetically-Modified Tomatoes Using Metabolomics for Objective Substantial Equivalence Assessment , 2011, PloS one.

[18]  Vikram Virdi,et al.  Role of plant expression systems in antibody production for passive immunization. , 2013, The International journal of developmental biology.

[19]  S. Fujii,et al.  Alpha-tomatine purification and quantification in tomatoes by HPLC , 1994 .

[20]  D. Iglesias,et al.  Proteomic analysis of "Moncada" mandarin leaves with contrasting fruit load. , 2013, Plant physiology and biochemistry : PPB.

[21]  S. Scheurer,et al.  Tomato profilin Lyc e 1: IgE cross‐reactivity and allergenic potency , 2004, Allergy.

[22]  Raoul J. Bino,et al.  A Liquid Chromatography-Mass Spectrometry-Based Metabolome Database for Tomato1 , 2006, Plant Physiology.

[23]  S. Scheurer,et al.  Molecular characterization and allergenic activity of Lyc e 2 (beta-fructofuranosidase), a glycosylated allergen of tomato. , 2003, European journal of biochemistry.

[24]  A. Granell,et al.  A multisite gateway-based toolkit for targeted gene expression and hairpin RNA silencing in tomato fruits. , 2009, Plant biotechnology journal.

[25]  P. Fraser,et al.  Metabolomics: a second-generation platform for crop and food analysis. , 2011, Bioanalysis.

[26]  Cathie Martin,et al.  A Visual Reporter System for Virus-Induced Gene Silencing in Tomato Fruit Based on Anthocyanin Accumulation1[C][W] , 2009, Plant Physiology.

[27]  E. Ibáñez,et al.  MS-based analytical methodologies to characterize genetically modified crops. , 2011, Mass spectrometry reviews.

[28]  R. Abagyan,et al.  XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification. , 2006, Analytical chemistry.

[29]  M. Rossignol,et al.  Proteomic analysis of MON810 and comparable non-GM maize varieties grown in agricultural fields , 2011, Transgenic Research.

[30]  Yan-yan Li,et al.  [Unintended effects assessment of genetically modified crops using omics techniques]. , 2013, Yi chuan = Hereditas.

[31]  R. Herman,et al.  Unintended compositional changes in genetically modified (GM) crops: 20 years of research. , 2013, Journal of agricultural and food chemistry.

[32]  Xin Lu,et al.  Metabolic profiling based on LC/MS to evaluate unintended effects of transgenic rice with cry1Ac and sck genes , 2012, Plant Molecular Biology.

[33]  R. Van Ree,et al.  Lipid Transfer Protein: A Pan-Allergen in Plant-Derived Foods That Is Highly Resistant to Pepsin Digestion , 2000, International Archives of Allergy and Immunology.

[34]  P. Fraser,et al.  Proteome changes in tomato lines transformed with phytoene synthase-1 in the sense and antisense orientations , 2012, Journal of experimental botany.

[35]  S. Mehrotra,et al.  Evaluation of designer crops for biosafety--a scientist's perspective. , 2013, Gene.

[36]  Nigel W. Hardy,et al.  Hierarchical metabolomics demonstrates substantial compositional similarity between genetically modified and conventional potato crops. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[37]  M. Oyama,et al.  Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection. , 2013, The Journal of clinical investigation.

[38]  A I Saeed,et al.  TM4: a free, open-source system for microarray data management and analysis. , 2003, BioTechniques.

[39]  S. Neumann,et al.  CAMERA: an integrated strategy for compound spectra extraction and annotation of liquid chromatography/mass spectrometry data sets. , 2012, Analytical chemistry.

[40]  K. Oksman-Caldentey,et al.  Unintended effects in genetically modified crops: revealed by metabolomics? , 2006, Trends in biotechnology.

[41]  Jian-Kang Zhu,et al.  Rapid phosphatidic acid accumulation in response to low temperature stress in Arabidopsis is generated through diacylglycerol kinase , 2013, Front. Plant Sci..

[42]  W. Weckwerth,et al.  Identification of putative new tomato allergens and differential interaction with IgEs of tomato allergic subjects , 2013, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[43]  Bertil Schmidt,et al.  Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment , 2008, BMC Bioinformatics.

[44]  Weiqing Zeng,et al.  Analytical method evaluation and discovery of variation within maize varieties in the context of food safety: transcript profiling and metabolomics. , 2014, Journal of agricultural and food chemistry.

[45]  Howard V. Davies,et al.  Comparison of Tuber Proteomes of Potato Varieties, Landraces, and Genetically Modified Lines1 , 2005, Plant Physiology.