Research and analysis

ACRE guidance: producing precision bred organisms

Published 27 February 2025

Applies to England

This is draft guidance. It is published for reference alongside the draft Genetic Technology (Precision Breeding) Regulations 2025.

The Genetic Technology (Precision Breeding) Act 2023 defines ‘precision bred organisms’ as plants or animals developed using modern biotechnology (such as genome editing), that contain genetic features that could also have been produced by traditional breeding processes.

This guidance discusses genetic features produced by techniques of modern biotechnology, which are used currently, and clarifies whether they would result in a precision bred organism. The scientific arguments and rationale for determining precision bred (PB) status apply to both plants and animals. However, the guidance is for those developing PB plants. This is because it accompanies regulations that implement the PB act for plants only. There are no implementing regulations for PB animals at this time.

This guidance will be updated to keep pace with scientific developments and user experience. It will replace  previous guidance associated with The Genetically Modified Organisms (Deliberate Release) (Amendment) (England) Regulations 2022, which will be revoked.

Those intending to release precision bred plants into the environment for non-marketing purposes (such as in research and development trials) must confirm that they have used this guidance when they submit their ‘release notice’ to Defra.  This notice will contain information about the:

• characteristics of the precision bred plants
• precision breeding techniques used to develop them
• type of genetic changes introduced

If the intention is to market a precision bred plant or food and feed derived from it, formal confirmation from Defra of precision bred status is required. This should be sought through the submission of a ‘marketing notice’ to Defra. Defra recommends strongly that developers read this guidance first. A separate, additional authorisation must be granted before food and feed derived from precision bred plants can be sold (Food Standards Agency).

More generally, confirmation from Defra that a plant is a precision bred organism will not enable it to be marketed unless it has met all the necessary regulatory requirements. This may include but is not limited to regulations made under the Plant Varieties and Seeds Act 1964, the Plant Varieties Act 1997, the Food Safety Act 1990, General Food Law, the Food Information Regulation and Assimilated Regulation (EC) 178/2002.    

1.  Scientific background

A large body of scientific evidence demonstrates that genetic material naturally exists in variant forms, even between or within individuals of the same species. Naturally occurring genetic variation is exploited by breeders to produce improved plant varieties. They use a range of techniques and interventions to generate and capture this genetic variation. Precision bred organisms contain these types of genetic changes.

2. Criteria

For a plant to be considered ‘precision bred’ it must meet criteria outlined in the Genetic Technology (Precision Breeding) Act 2023. The act defines a precision bred organism as a plant containing any stable genomic feature arising from the application of modern biotechnology that could also have arisen through traditional processes.

The act defines a list of traditional processes that covers the range of genetic changes that could feasibly occur in plants over the course of their lifetime or in a conventional breeding programme. Alterations may be introduced in the DNA sequence and, or, the epigenome, including both nuclear and non-nuclear genomes. Naturally occurring changes range from point mutations, which may arise from mistakes in DNA polymerase activity, to chromosomal translocations arising from mis-segregation of chromosomes during replication.

There is no specific limit to the number or size of genomic alterations that can be made within a single precision bred organism. However, those using this guidance should consider whether the alterations introduced could have arisen in their plant using traditional breeding processes. Precision bred organisms cannot contain transgenic material, including editing cassettes, selectable markers and vector genes. Transgenic intermediates produced to enable the editing process may be used so long as all transgenic sequences are removed prior to release or marketing. Transgenic sequences are those that could not arise naturally or through traditional breeding practices.

The act stipulates that genetic changes introduced by modern biotechnology must be stable. Thus, developers should demonstrate that genetic changes made are capable of being inherited following either sexual or asexual reproduction. Developers are not expected to monitor or prevent the accumulation of natural mutations in precision bred organisms following confirmation of precision bred status.

The act establishes that Copy Number Variation (CNV), epigenetic status, and location of genetic changes made will not impact the determination of precision bred status. This is because CNV is known to have significant natural variation within populations and does not directly correlate to protein expression and trait development. Similarly, epigenetic status varies across the lifetime of plants.

Genome location is not a criterion that affects PB status because spontaneous mutations occur throughout genomes over time. Similarly induced mutations, such as those arising from traditional processes, also occur randomly throughout genomes. Whilst the location of genomic alterations is not required for release notices developers are likely to have gathered such data in order to comply with the information required within a marketing notification.  

The next sections provide examples of more specific cases in which modern biotechnologies may be applied to produce precision breeding outcomes.

3. Site Directed Nucleases (SDNs)

3.1 SDN1-type changes to genetic material

Precision bred plants may be developed using Site Directed Nucleases (SDNs). These genome editing systems (such as CrisprCas9) can create DNA strand breaks at specific locations within a genome. In SDN1, the strand break is repaired by endogenous DNA mechanisms, usually non-homologous end joining (NHEJ).

NHEJ is an error prone repair mechanism that often results in small insertions or deletions (indels) to the DNA sequence. These indels may alter the function of a protein or affect the action of non-protein coding regulatory sites. Single or double strand breaks followed by repair through endogenous repair mechanisms like NHEJ is one of the processes that naturally produces spontaneous mutations during the lifetime of a plant. This aligns with the ‘traditional processes’ set out in the Genetic Technology Act 2023. As a result, plants developed using SDN1 would likely be considered precision bred organisms.

Developers may also use SDN1 to target multiple sites at once, to generate lesions at two or more spatially separated locations within a chromosome. In this way, larger stretches of DNA can be deleted or inverted, potentially removing one or more whole genes or non-coding regions. This approach can result in significant rearrangements, deletions, or translocations of genetic material. These are events that also occur and can be selected for when using traditional breeding techniques, where they may be mediated by agents such as transposons or other mutagens.

3.2 SDN2 and SDN3

Developers may wish to use other cellular mechanisms, such as Homology Directed Repair (HDR) to change specific sequences within the genome of an organism. SDN2 and SDN3 also create strand breaks at a predetermined location. However, inclusion of a DNA template allows exploitation of HDR, which directs the DNA repair machinery to generate the precise sequence change that is required. SDN2 results in smaller sequences changes or corrections, whilst SDN3 results in the targeted insertion of longer stretches of genetic material, such as a whole gene or several contiguous genes.

SDN2 directly exploits existing cellular mechanisms that may be used when repairing spontaneous mutations that occur in a plant genome and therefore aligns with the ‘traditional processes’ set out in the Genetic Technology (Precision Breeding) Act 2023. As a result, plants developed using SDN2 could be considered precision bred organisms as long as functional transgenes such as selectable markers and vectors are no longer present, and the genetic changes are the same as those that could have resulted from traditional processes.

Provided that the gene sequence that is inserted could have been crossed from within the existing gene pool of the organism, SDN3 potentially produces outcomes that are the same as those that might arise through one of the ‘traditional processes’ set out in the act.

3.3 Prime or base editing

Using an adaptation of the approach described above, it is possible to precisely direct which specific nucleotide or nucleotides are changed within a genome, without generating a double strand DNA break. To achieve this, an SDN such as CrisprCas9 is modified so that it nicks one of the DNA strands at a predetermined location. An enzyme linked to the SDN converts the incumbent nucleotide to an alternate one. As with SDN1, base editing makes the same type of genetic changes that occur naturally and are already exploited by breeders using traditional methods when selecting for varieties that have specific single nucleotide polymorphisms (SNPs).

This guidance does not provide a numerical upper threshold on the number of SNPs that may be introduced. However, developers should take into consideration how many SNPs could accumulate in a traditional breeding programme.

4. Recombinant DNA techniques

4.1 Cisgenic changes to genetic material

Cisgenesis involves the introduction of genetic material from a sexually compatible donor species into a recipient. Unlike SDN3, older style cisgenic techniques require construction of a recombinant vector outside of the host organism, which is then integrated into the genome at a random location. Cisgenes generally include all the naturally occurring genetic elements observed in the donor species, including introns and the native promoters and terminators. They also generally require short left and right borders, such as T-DNA borders, to enable insertion.

Plants created using cisgenic techniques are considered precision bred organisms if the genetic material inserted could have been bred into the organism by traditional processes. This applies regardless of whether the inserted sequence was cloned from a donor organism or synthesised using knowledge of the contiguous sequences involved. The presence of left and right border sequences, such as T-DNAs, does not preclude an organism from being considered precision bred so long as the notifier can justify that the organism already contains, or could be crossed with a species that contains T-DNA, or sequences with high homology to T-DNAs. Provided this can be demonstrated, cisgenesis produces outcomes that are the same as those that might arise through ‘sexual fertilisation or polyploidy induction’ and therefore could have been produced by ‘traditional processes’ as set out in the act.

A precision bred plant may contain multiple cisgenes at a single locus or single cisgenes at multiple loci. Whilst there is no specific limit on the number of cisgenes that may be introduced at once, developers should consider whether this is consistent with the genetic variation that could occur naturally within sexually compatible relatives or as a result of traditional processes and selection.

4.2 Intragenic changes to genetic material

Intragenic changes to genetic material also involve the in vitro manipulation of a nucleic acid molecule followed by its insertion into the genome using recombinant DNA technology. The main difference between intragenesis and cisgenesis is that intragenesis generally involves exon or intron swapping or splicing, or creation of a recombinant DNA molecule with the coding region of one gene associated with the non-coding regulatory domains of one, or several, different genes. Importantly, by definition, in intragenesis all these genetic elements are derived from species which are sexually compatible with one another.

The traditional processes outlined in the act are unlikely to result in the highly specific shuffling of intragenic regions and their regulatory domains to create novel splice variants with regulatory domains from unrelated genes. As a result, they are unlikely to meet the criteria for a precision bred organism as described in the act. However, demonstration of a strong rationale that the genetic changes could have arisen through traditional processes will be considered. Examples may include circumstances where the developer has produced recombinant DNA representing the complete coding region of a gene, alongside regulatory domains that feasibly could come to control the inserted gene (for example, through translocation).

5. Summary

Plants containing the type of genetic changes resulting from intragenesis are unlikely to be considered precision bred unless a strong rationale for this is provided. Meanwhile, plants containing changes resulting from cisgenesis or SDNs are likely to be considered precision bred organisms, so long as:

• functional transgenes such as selectable markers and vectors have been removed (for example, by segregation)
• the genetic changes are the same as those that could have resulted from traditional processes and selection

Some possible exemptions are:

• where numerous genomic alterations have been made simultaneously, developers should consider whether the amount of introduced genetic variation could arise naturally or be introduced through a breeding programme

• genomic changes that result in sequences or traits that could not reasonably be expected to arise through traditional processes, such as conversion of an endogenous protein to a humanised version of this protein, would not be considered precision bred organisms

If you are uncertain whether a specific organism generated using a genetic technology such as gene editing would be considered a precision bred organism, you should contact Defra by emailing the Genetic Technologies Policy and Regulation Team at genetictechnologies@defra.gov.uk.