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Identification of potentially hazardous human gene products in GMO risk assessment

Published online by Cambridge University Press:  03 April 2008

Hans Bergmans ,
Colin Logie ,
Kees Van Maanen ,
Harm Hermsen ,
Michelle Meredyth  and
Cécile Van Der Vlugt
Hans Bergmans
Affiliation:
GMO Office, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
Colin Logie
Affiliation:
Nijmegen Department of Molecular Biology, Nijmegen Center for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands
Kees Van Maanen
Affiliation:
Animal Health Service, Deventer, The Netherlands
Harm Hermsen
Affiliation:
Centre for Biological Medicines and Medical Technology, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
Michelle Meredyth
Affiliation:
Departments of Genomics, Biotech and Internal Medicine I, Technical University Dresden, Germany
Cécile Van Der Vlugt
Affiliation:
GMO Office, National Institute for Public Health and the Environment, Bilthoven, The Netherlands

Abstract

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Genetically modified organisms (GMOs), e.g. viral vectors, could threaten the environment if by their release they spread hazardous gene products. Even in contained use, to prevent adverse consequences, viral vectors carrying genes from mammals or humans should be especially scrutinized as to whether gene products that they synthesize could be hazardous in their new context. Examples of such potentially hazardous gene products (PHGPs) are: protein toxins, products of dominant alleles that have a role in hereditary diseases, gene products and sequences involved in genome rearrangements, gene products involved in immunomodulation or with an endocrine function, gene products involved in apoptosis, activated proto-oncogenes. For contained use of a GMO that carries a construct encoding a PHGP, the precautionary principle dictates that safety measures should be applied on a “worst case” basis, until the risks of the specific case have been assessed. The potential hazard of cloned genes can be estimated before empirical data on the actual GMO become available. Preliminary data may be used to focus hazard identification and risk assessment. Both predictive and empirical data may also help to identify what further information is needed to assess the risk of the GMO. A two-step approach, whereby a PHGP is evaluated for its conceptual dangers, then checked by data bank searches, is delineated here.

Keywords

genetic modificationgenetic engineeringgenetically modified organismGMOcontained userisk assessmenthazard identificationGMO regulationviral vectorhuman gene products
Type
Research Article
Information
Environmental Biosafety Research , Volume 7 , Issue 1 , January 2008 , pp. 1 - 9
Copyright
© ISBR, EDP Sciences, 2008

References

ACGM (2000) Compendium of Guidance from the UK Health and Safety Commission's Advisory Committee on Genetic Modification. Health & Safety Executive, London
Allen, JE, Salzberg, SL (2005) JIGSAW: integration of multiple sources of evidence for gene prediction. Bioinformatics 21: 3596–3603 CrossRef
Barreto, V, Marques, R, Demengeot, J (2001) Early death and severe lymphopenia caused by ubiquitous expression of the Rag1 and Rag2 genes in mice. Eur. J. Immunol. 31: 3763–3772 3.0.CO;2-Y>CrossRef
Berg, P, Baltimore, D, Brenner, S, Roblin, RO III, Singer, XF (1975) Summary statement of the Asilomar conference on recombinant DNA molecules. Proc. Natl. Acad. Sci. USA 72: 1981–1984 CrossRef
Dull, T, Zufferey, R, Kelly, M, Mandel, RJ, Nguyen, M, Trono, D, Naldini, L (1998) A third-generation lentivirus vector with a conditional packaging system. J. Virol. 72: 8463–8471
EU (1998) Council Directive 98/81/EC of 26 October 1998, amending Directive 90/219/EEC on the contained use of genetically modified micro-organisms. Off. J. Eur. Comm. 05.12.1998: L 330/13
EU (2000) Commission Decision of 27 September 2000 concerning the guidance notes for risk assessment outlined in Annex III of Directive 90/219/EEC an the contained use of genetically modified micro-organisms, 2000/608/EC. Off. J. Eur. Comm. 12.10.2000: L 258/43
EU (2001) Directive 2001/18/EC of the European Parliament and of the Council of 12 March 2001 on the deliberate release into the environment of genetically modified organisms and repealing Council Directive 90/220/EEC. Off. J. Eur. Comm. 17.4.2001: L 106/1
EU (2002) Commission decision of 24 July 2002 establishing guidance notes supplementing Annex II to Directive 2001/18/EC of the European Parliament and of the Council on the deliberate release into the environment of genetically modified organisms and repealing Council Directive 90/220/EEC, 2002/623/EC. Off. J. Eur. Comm. 30.7.2002: L 200/22
Fallaux, FJ, Bout, A, Van der Velde, I, Van den Wollenberg, DJ, Hehir, KM, Keegan, J, Auger, C, Cramer, SJ, Van Ormondt, H, Van der Eb, AJ, Valerio, D, Hoeben, RC (1998) New helper cells and matched early region 1-deleted adenovirus vectors prevent generation of replication-competent adenoviruses. Hum. Gene Ther. 9: 1909–1917 CrossRef
Fry, BG (2005) From genome to “venome”: Molecular origin and evolution of the snake venom proteome inferred from phylogenetic analysis of toxin sequences and related body proteins. Genome Res. 15: 403–420 CrossRef
Han, JS, Szak, ST, Boeke, JD (2004) Transcriptional disruption by the L1 retrotransposon and implications for mammalian transcriptomes. Nature 249: 268–274 CrossRef
HSE (2002) Interim guidance on risk assessment of genetically modified micro-organisms eliciting altered immune responses. HSE Newsletter 31, Health & Safety Executive, London
Hubbard, T, Andrews, D, Caccamo, M, Cameron, G, Chen, Y, Clamp, M, Clarke, L, Coates, G, Cox, T, Cunningham, F, Curwen, V, Cutts, T, Down, T, Durbin, R, Fernandez-Suarez, XM, Gilbert, J, Hammond, M, Herrero, J, Hotz, H, Howe, K, Iyer, V, Jekosch, K, Kahari, A, Kasprzyk, A, Keefe, D, Keenan, S, Kokocinsci, F, London, D, Longden, I, McVicker, G, Melsopp, C, Meidl, P, Potter, S, Proctor, G, Rae, M, Rios, D, Schuster, M, Searle, S, Severin, J, Slater, G, Smedley, D, Smith, J, Spooner, W, Stabenau, A, Stalker, J, Storey, R, Trevanion, S, Ureta-Vidal, A, Vogel, J, White, S, Woodwark, C, Birney, E (2005) Ensembl 2005. Nucl. Acids Res. 33: D447–D453 CrossRef
Jackson, RJ, Ramsay, AJ, Christensen, CD, Beaton, S, Hall, DF, Ramshaw, IA (2001) Expression of Mouse Interleukin-4 by a Recombinant Ectromelia Virus Suppresses Cytolytic Lymphocyte Responses and Overcomes Genetic Resistance to Mousepox. J. Virol. 75: 1205–1210 CrossRef
Mazière, P, Enright, AJ (2007) Prediction of microRNA targets. Drug Discov. Today 12: 452–458 CrossRef
NIH (2002) NIH Guidelines for research involving recombinant DNA molecules. National Institutes of Health, Bethesda
OECD (1986) Recombinant DNA safety considerations. OECD, Paris
Stalker, J, Gibbins, B, Meidl, P, Smith, J, Spooner, W, Hotz, H-R, Cox, AV (2004) The Ensembl Web Site: Mechanics of a Genome Browser. Genome Res. 14: 951–955 CrossRef
Tanino, M, Debily, M-A, Tamura, T, Hishiki, T, Ogasawara, O, Murakawa, K, Kawamoto, S, Itoh, K, Watanabe, S, de Souza, SJ, Imbeaud, S, Graudens, E, Eveno, E, Hilton, P, Sudo, Y, Kelso, J, Ikeo, K, Imanishi, T, Gojobori, T, Auffray, C, Hide, W, Okubo, K (2005) The Human Anatomic Gene Expression Library (H-ANGEL), the H-Inv integrative display of human gene expression across disparate technologies and platforms. Nucl. Acids Res. 33: D567–D572
Yoo, S, McKee, BD (2004) Overexpression of Drosophila Rad51 protein (DmRad51) disrupts cell cycle progression and leads to apoptosis. Chromosoma 113: 92–101 CrossRef