title: Characteristics and safety assessment of intractable proteins in genetically modified crops.
abstract: Genetically modified (GM) crops may contain newly expressed proteins that are described as "intractable". Safety assessment of these proteins may require some adaptations to the current assessment procedures. Intractable proteins are defined here as those proteins with properties that make it extremely difficult or impossible with current methods to express in heterologous systems; isolate, purify, or concentrate; quantify (due to low levels); demonstrate biological activity; or prove equivalency with plant proteins. Five classes of intractable proteins are discussed here: (1) membrane proteins, (2) signaling proteins, (3) transcription factors, (4) N-glycosylated proteins, and (5) resistance proteins (R-proteins, plant pathogen recognition proteins that activate innate immune responses). While the basic tiered weight-of-evidence approach for assessing the safety of GM crops proposed by the International Life Sciences Institute (ILSI) in 2008 is applicable to intractable proteins, new or modified methods may be required. For example, the first two steps in Tier I (hazard identification) analysis, gathering of applicable history of safe use (HOSU) information and bioinformatics analysis, do not require protein isolation. The extremely low level of expression of most intractable proteins should be taken into account while assessing safety of the intractable protein in GM crops. If Tier II (hazard characterization) analyses requiring animal feeding are judged to be necessary, alternatives to feeding high doses of pure protein may be needed. These alternatives are discussed here.
authors.affiliation: Bayer CropScience, 2 T.W. Alexander Drive, P.O. Box 12014, Research Triangle Park, NC 27709-2014, USA. Electronic address: dean.bushey@bayer.com.
authors.forename: Dean F
authors.initials: DF
authors.lastname: Bushey
authors.affiliation: Monsanto Company, Global Regulatory, 800 North Lindbergh Boulevard, St. Louis, MO 63167, USA.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Bannon
authors.affiliation: DuPont Pioneer, 7300 NW 62nd Avenue, P.O. Box 1004, Johnston, IA 50131, USA.
authors.forename: Bryan F
authors.initials: BF
authors.lastname: Delaney
authors.affiliation: Syngenta Biotechnology, Inc., P.O. Box 12257, 3054 East Cornwallis Road, Research Triangle Park, NC 27709-2257, USA.
authors.forename: Gerson
authors.initials: G
authors.lastname: Graser
authors.affiliation: Centre for Biologics Research, Sir Frederick G. Banting Research Centre, 251 Promenade Sir Frederick Banting Driveway, Ottawa, Ontario K1A 0K9, Canada.
authors.forename: Mary
authors.initials: M
authors.lastname: Hefford
authors.affiliation: BASF Plant Science, L.P., Regulatory Science, 26 Davis Drive, Research Triangle Park, NC 27709-3528, USA.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Monsanto Company, Global Regulatory, 800 North Lindbergh Boulevard, St. Louis, MO 63167, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Lee
authors.affiliation: Dow AgroSciences, 9330 Zionsville Road, Indianapolis, IN 46268, USA.
authors.forename: Krishna M
authors.initials: KM
authors.lastname: Madduri
authors.affiliation: Department of Food Science, University of Wisconsin-Madison, 1550 Linden Drive, Madison, WI 53706, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Pariza
authors.affiliation: BASF Plant Science, L.P., Regulatory Science, 26 Davis Drive, Research Triangle Park, NC 27709-3528, USA.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Privalle
authors.affiliation: Bayer CropScience, 2 T.W. Alexander Drive, P.O. Box 12014, Research Triangle Park, NC 27709-2014, USA.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Ranjan
authors.affiliation: Departamento de Ingeniería Celular y Biocatálisis, Instituto de Biotecnología, Universidad Nacional Autónoma de México, AP 510-3, CP 62250 Cuernavaca, Morelos, Mexico.
authors.forename: Gloria
authors.initials: G
authors.lastname: Saab-Rincon
authors.affiliation: Dow AgroSciences, 9330 Zionsville Road, Indianapolis, IN 46268, USA.
authors.forename: Barry W
authors.initials: BW
authors.lastname: Schafer
authors.affiliation: University of Missouri, Division of Biochemistry, Christopher S. Bond Life Sciences Center, Columbia, MO 65211, USA.
authors.forename: Jay J
authors.initials: JJ
authors.lastname: Thelen
authors.affiliation: DuPont Pioneer, 7300 NW 62nd Avenue, P.O. Box 1004, Johnston, IA 50131, USA.
authors.forename: John X Q
authors.initials: JX
authors.lastname: Zhang
authors.affiliation: DuPont Pioneer, 7300 NW 62nd Avenue, P.O. Box 1004, Johnston, IA 50131, USA.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Harper
mesh_terms: D000821:Animal Feed; D000818:Animals; D003257:Consumer Product Safety; D018556:Crops, Agricultural / Q000235:genetics*; D030841:Food, Genetically Modified; D010940:Plant Proteins / Q000235:genetics*; D030821:Plants, Genetically Modified / Q000235:genetics*; D018570:Risk Assessment; D012449:Safety
chemical_list: D010940:Plant Proteins
keywords: Food safety; Genetically modified (GM) crops; Intractable proteins; Membrane proteins; N-glycosylated proteins; Resistance proteins; Signaling proteins; Transcription factors; Weight-of-evidence approach