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The nationally consistent legislative scheme for gene technology is comprised of the Commonwealth Gene Technology Act 2000 and Gene Technology Regulations 2001, and corresponding State and Territory legislation.

The Commonwealth Gene Technology legislation took effect on 21 June 2001 and consists of the following:

• ��(current compilation)
• ��(current compilation)

Further information regarding the national regulatory scheme and the corresponding legislation for the states and territories is available on��.

The corresponding South Australian Legislation is:

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Researchers who apply for an OGTR licence for dealings involving intentional release (DIR) of genetically modified (GM) plants into the environment under limited and controlled conditions need to be compliant with the��.

Pursuant to sections 5(1)(a)(ii) and 5A(1) of the above Act, areas of the State may be designated in which no genetically modified food crops may be cultivated.

Exemptions for certain activities may be permitted under the Act for field trials of GM food crops to occur in some areas.

Please contact the��Research Compliance Officers��for further information.

Dealings with viral vectors can be classified in the DNIR, NLRD or Exempt categories depending on the nature of the viral vectors used. The Regulator has developed�� to assist.

The Regulator has clarified that when considering whether a genetic modification confers an immunomodulatory effect, the intention is to only include proteins, nucleic acid sequences or other molecules which either up-regulate or down-regulate the normal host immune response following exposure to an antigen.

Cytokines that alter the normal immune response would be considered immunomodulatory. An example would be an oncolytic virus that expresses a cytokine intended to amplify an anti-tumour immune response.

Antigens expressed for the purpose of vaccination are not considered immunomodulatory, as they initiate a normal immune response.

Allergens inducing an allergic response would also not be immunomodulatory, as that response is normal in a susceptible person. A GM microorganism expressing a common allergen could still require a licence under Schedule 3.1 (f) as the genetic modification would increase the capacity of the organism to cause harm.

Gene drives are genetic elements that are favoured for inheritance. An organism that contains a gene drive due to gene��technology will be a GMO. It will be subject to regulation under the Act.

Contained dealings with GMOs containing functional gene drives need a��DNIR licence.

Dealings with viral vectors that can change an organism to produce an engineered gene drive also need a��DNIR licence.

Gene editing technology involves the use of site directed nucleases (SDNs) to create genetic changes. SDNs include, but are not limited to, CRISPR/Cas9, zinc finger nucleases, meganucleases and TALENs.

The regulation of genome editing technology is defined by the presence or absence of a nucleic acid template used to achieve homologous recombination.

• Where foreign nucleic acid is inserted, or a nucleic acid template is used, the technology will always be regulated.

SDN-1 gene editing

• SDN-1��involves genome breaks��without a supplied template��for repair.
• It can be used to create organisms with small genetic changes.
• Utilises non-homologous end joining.
• No foreign DNA is inserted.

The GMO status of SDN-1 gene edited organisms, and the IBC approval required prior to commencing work with them, is shown in this��genome editing summary table

GMOs which may subsequently by classed as "not a GMO"

There are scenarios (shown in yellow in the gene editing table) when nucleic acid is introduced into the initial organism as a transgene, but the initial organism or its offspring may subsequently be classed as “not a GMO” under certain circumstances (see examples below). Contact the IBC for further guidance or to apply for release of these organisms.

• Example 1: A plant line with stably integrated Cas9 and gRNA transgenes is a GMO, but those of its segregating offspring which carry a SDN-1 modification and that lack Cas9 and gRNA transgenes or other traits from gene technology would not be GMOs.
• Example 2: Cas9 and gRNA are transiently expressed in an organism. The organism is a GMO while the transgenes and their products are present. If the transient transgene and its expressed products have degraded over time and only SDN-1 modifications remain, the organism and its offspring are not GMOs.

In both cases,��initial IBC approval is required to undertake the modification, and��you require IBC confirmation prior to release from containment.

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Prime editing

• Relies upon a site-directed nuclease with an additional enzymatic function (reverse transcriptase) engineered in. ��
• Regulated as a gene technology dealing requiring approval unless another exclusion under Schedule 1 applies.

Base editing

• Base editing requires additional enzyme activity, e.g. cytidine deaminase or adenine deaminase to achieve changes to nucleic acids in addition to nuclease activity.
• Always regulated as a gene technology dealing requiring approval unless another exclusion under Schedule 1 applies.

Under��Item 11 of Schedule 1A��of the Gene Technology Regulations,��some RNAi techniques are��not��considered gene technology, meaning organisms modified using these methods are��not classified as GMOs.

These exclusions apply when RNA molecules are introduced to an organism to temporarily induce gene silencing. Examples of delivery methods include:

• Externally applied RNA such as by spraying with or dipping in an RNA solution
• injecting RNA into the organism
• electroporation
• an organism consuming material to which the RNA has been applied, such as (e.g. insects consuming RNA-treated plant material.

To qualify as not being classified as gene technology, the RNAi technique must meet all of the following criteria:

1. The organism’s genomic DNA sequence cannot be changed by the technique
   • The RNA must not cause permanent genomic changes
   • Epigenetic changes (such as DNA methylation) are permitted.��
2. No potential to produce infectious agents; and
3. The introduced RNA cannot be translated into a protein.

If these conditions are met, the RNA molecules used may include:

• Small interfering RNAs (siRNAs)
• Artificial microRNAs
• Short or long double-stranded RNAs
• Hairpin RNAs

These can be sequences of any origin.��

This exclusion does not apply to RNAi techniques involving stable or transient transformation of the organism with a transgene that expresses RNA to induce gene silencing. Such organisms remain regulated under the Gene Technology Act 2000.

Introducing antisense oligonucleotides (ASOs) into an organism to modulate endogenous gene expression is not considered gene technology, if the following conditions are met.

This includes:

• Morpholinos
• Splice-switching oligonucleotides
• DNA oligonucleotides that cannot be transcribed

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To ensure the use of ASOs is not classified as gene technology, all the following must apply:

(a) the introduction of the nucleic acid or nucleic acid analogue does not result in an alteration of the organism’s genome sequence; and

(b) the introduction of the nucleic acid or nucleic acid analogue cannot give rise to an infectious agent; and

(c) in the case of nucleic acid or nucleic acid analogue that is DNA—the DNA cannot be transcribed.

Transfer of nuclei, plastids or mitochondria (whether between cells of the same species or of different species) may be classed as not gene technology if the transfer does not involve any genetically modified material.��