Application to Develop* genetically modified organisms in containment Under section 40(1)(b) of the HSNO Act 1996 (excluding rapid assessment) *“Develop” includes developing, fermenting and regenerating genetically modified organisms BP House 20 Customhouse Quay PO Box 131, Wellington Phone: 04-916 2426 Fax: 04-914 0433 Email: [email protected] Web: www.ermannz.govt.nz ER-AF-N03-4 09/09 Please note This application form covers the development of genetically modified organisms that: 1. Do not meet Category A and/or B experiments as defined in the HSNO (Low- Risk Genetic Modification) Regulations 2003; 2. Occur either in a containment structure (i.e. laboratory) or outdoors within a containment facility; or 3. Otherwise cannot undergo a rapid assessment for low-risk genetic modification. Any extra material that does not fit in the application form must be clearly labelled, cross-referenced, and included as appendices to the application form. Commercially sensitive information must be collated in a separate appendix. You should justify why you consider the material commercially sensitive, and make sure it is clearly labelled as such. If technical terms are used in the application form, simply explain these terms in the Glossary (Section 8 of this application form). Unless otherwise indicated, all sections of this form must be completed for the application to progress. Applicants must sign the application form and enclose the correct application fee (including GST). The application fee can be found in our published Schedule of Fees and Charges on the ERMA New Zealand website. We are unable to process applications that do not contain the correct application fee. An electronic and paper copy of the final completed form must be submitted. If you have any queries regarding the information required or would like to discuss your draft application form, please contact a New Organisms Advisor at ERMA New Zealand. This form was approved by the Chief Executive of ERMA New Zealand on 22 September 2009. This form replaces all previous versions. Page 2 of 19 Section 1: Application details a) Application title Genetic modification of animal and human cell lines for research and teaching purposes b) Organisation name University of Otago c) Postal Address Department of Microbiology and Immunology, University of Otago P O Box 56 Dunedin Page 3 of 19 Section 2: Summary of application a) Provide a plain English summary of this application including: . Explain the purpose of your research in the context of your organisation’s history and goals. The purpose of the application (e.g. what is the research you wish to perform and why do you consider that it is important? what are the benefits of this research?). If there are any alternative methods to achieve the aims of this research, explain why you wish to perform the research this way. Describe the project you wish to undertake (section 40(2)(a)(ii) of the HSNO Act). Are you aware of any possible adverse effects of the organism on the environment? If so, any potential mitigation measures? . Where do you intend to conduct these activities? Are there specific location(s) or are you seeking approval for all of New Zealand? . How do other legislative requirements apply to your proposed activities? (e.g. the Resource Management Act, the Medicines Act. If this application is for a development outdoors within a containment facility, discuss why your activities are not “field testing” activities for the purpose of the HSNO Act. If technical terms are used here or elsewhere in the application, add simple explanations for these terms in the Glossary (Section 8 of this application form). The University of Otago is a research-intensive university. This application seeks approval to genetically modify animal and human cell lines to provide researchers and students with tools to explore the role and function of genes. These develpoments will underpin research into distinct areas of biology but are unified by their use of standard laboratory methodology, including the use plasmids and replication-deficient viral vectors, to transfer nucleic acids into animal or human cell lines. The ability to genetically modify these cell lines in this way will help researchers to determine gene function, and more specifically how individual genes and groups of genes influence biological processes in vivo. This research is designed to generate and apply new knowledge of processes involved in: 1. Cell growth, metabolism, differentiation and development; 2. Biological responses to environmental and chemical stress; 3. Host-pathogen and host-commensal interactions; and 4. The causation of disease The animal and human cell lines to be modified will be established cell lines obtained from commercial sources or from reputable scientific laboratories, or will be primary cell lines developed with the approval of an appropriate Ethics Committee. The cell lines may include embryonic stem cell and induced pluripotent stem cell lines of animal species and induced pluripotent stem cell lines derived from humans, but will not include embryonic stem cell lines derived from humans. In many cases the genetic manipulation will involve a complete gene sequence from one species being introduced into a cell line derived from the same or a different species to enable changes in the biology or biochemistry of the recipient cell line to be correlated with the function of the transferred gene. In some cases DNA sequences will be introduced into a cell line to investigate function by silencing endogenous genes within that host. A further scientific goal of this research involves expression of genes by modified cell lines to allow purification and biochemical characterisation of recombinant proteins, or to produce replication-deficient viral vectors. In other cases, “reporter” genes will be introduced into a cell line in order to allow the expression of a gene within it to be monitored by various techniques (e.g. fluorescent microscopy for cell lines expressing green fluorescent protein) that detect expression of the reporter gene. The broad nature of these studies requires approval to modify a wide range of animal and Page 4 of 19 human cell lines with a variety of genes from different organisms. However in all cases the modifications will be restricted by virtue of the fact that genes transferred to any cell line will not lead to the production of infectious particles such as prions or replication-competent viruses and will not increase the risk of the cell lines to humans. The cell lines are completely reliant on human intervention for survival and would not survive outside of controlled conditions in the laboratory. Therefore, the nature of containment is such that the risk of escape and subsequent infection is negligible. The benefits from the development of these cell lines will be to add to the body of scientific knowledge of processes involved in growth, metabolism, differentiation, disease and response to stress, and knowledge that may lead to the development of new treatments or diagnostic tools for various diseases of humans and animals. b) Provide a short summary statement of the purpose of this application to be used on ERMA New Zealand’s public register This statement must be a maximum of 255 characters including spaces and punctuation. If native or human genetic material directly obtained from New Zealanders is to be used, include this information here. Sufficient details must be provided to enable the Authority to provide the information required in the register under section 20(2)(c) of the HSNO Act. To develop genetically modified cultured animal and human cell lines for research and teaching purposes to generate knowledge of processes involved in growth, metabolism, differentiation, development, stress response and disease. Page 5 of 19 Section 3: The proposed organism(s) to be developed Section 2(1) of the HSNO Act defines what “identification” is. You must provide sufficient information to fulfill the criteria listed in the HSNO Act to enable the Authority to uniquely identify the organism in the register (as required in section 20(2)(b) of the HSNO Act). As per sections 40(2)(a)(i)-(iv) of the HSNO Act, you must: . Identify the new organism(s) (at the appropriate taxonomic level). Hint — you could start by discussing the characteristics of the host organism and then how the proposed genetic modifications are expected to alter these characteristics. Describe the project and the experimental procedures to be used. Provide details of biological material to be used. Provide details of the expression of foreign nucleic acid (if relevant). You must describe the biological characteristics of the new organism(s). The information should be relevant to: . The hazardous nature of the organism(s) that you are aware of. For example, is it a bacterium that can cause disease in plants or humans? Will the modifications enhance the pathogenicity of a microorganism? . Which of its characteristics may enable it to escape from containment? For example, can it produce air-disseminated spores? Can it dig under fences? Can it jump or fly over high fences? . The ability of the organism(s) to form an undesirable self-sustaining population and how easy such a population could be eradicated (section 43(b) of the HSNO Act). Organisms A. Animal cell lines derived from the species listed in Appendix 1. B. Human cell lines. The animal and human cell lines to be modified will be established cell lines obtained from commercial sources or from reputable scientific laboratories, or will be primary cell lines. Primary cell lines will be developed with the approval of an appropriate Ethics Committee and following appropriate Maori consultation or will be obtained from commercial sources or from reputable overseas scientific laboratories that developed the lines under ethical approval. The cell lines to be developed may include stem cell lines, including embryonic stem cell lines and induced pluripotent stem cells of animal species and induced pluripotent stem cells derived from humans, but will not include human embryonic stem cell lines.