CRISPR/Cas9 nucleases have been extensively used in chicken somatic and embryonic cells. Using an enrichment system, effective gene disruptions of PPAR, ATP5E, and OVA were obtained in chicken somatic cells DF-1 (Abu-Bonsrah et al., 2016) and embryonic stem cells (Zhang et al., 2017). In vivo disruption of the PAX7 gene in somites of early amniotic embryos was also reported (Ve’ron et al., 2015) by direct electroporation. These studies indicated varying knockdown efficiencies of 15%–41% which could be mainly relates to transfection approaches and cell systems (Zuo et al., 2017). Compared to human and mouse cells, the efficiency of customised gene editing in poultry and livestock is relatively low, which is the most significant barrier to developing transgenic animals for agriculture.

The electroporation technique, which is widely used in the chicken embryo, also results in the mosaic expression of constructs, which, when combined with loss-of-function approaches, could provide advantages compared to those observed in the fruit fly. However, gene inactivation in the chicken has been limited to knockdown by RNA interference and morpholino-based methodologies (Serralbo et al., 2013) each of which has its limitations, such as variable knockdown levels, off-target effects, and transient inhibition of transcripts.

This technology will permit the refinement of the spatial and temporal roles of genes during embryogenesis. Furthermore, this paves the way for future genetic manipulations of avian species. Indeed, recent reports of genetically modified chickens using targeted gene knockout utilising TALEN technology in isolated chicken PGCs indicate that the same strategy combined with the simpler CRISPR technique may soon be used on a large scale to generate specific genome-edited avian lines.

The domestication of poultry began over 8,000 years ago, and genetics has since improved the efficiency of meat and egg producing chickens (Eriksson et al., 2008). However, because male layers grow inefficiently for meat, newly hatched males are culled soon after hatching, creating serious ethical and economic issues. The industry therefore seeks methods to identify male embryos before hatching, ideally at the time of lay. In fact, United Egg Producers pledged to end male chick culling by 2020. Sex determination in birds is well studied (Graves, 2009), but while mechanisms are understood, the exact male-determining trigger remains unclear. Gene editing now offers promising solutions by inserting marker genes into the Z chromosome. Since males (ZZ) carry two Z chromosomes and females (ZW) only one, engineered females carrying a marked Z chromosome would produce male offspring with detectable markers, while females remain unmodified (Doran et al., 2017).Recently, engineered the “Holy Grail” (HG) system to selectively block male embryo development by inserting a genetic construct into the Z chromosome. The construct includes three genes expressed sequentially: a GFP “safe-lock,” an optogenetic switch, and Noggin. Flippase excises GFP, blue light activates Cre recombinase, and Noggin expression inhibits the BMP pathway, halting male development. Two transgenic lines were generated via CRISPR/Cas9: one carrying HG and another expressing Flp. Crosses produced ZFlpO/ZHG-SL males whose blue light treated eggs yielded only healthy female chicks. The system ensures 100% male elimination, aligning seamlessly with hatchery practices (Cohen et al., 2023). Marker genes, such as green fluorescent protein, could allow rapid, non-invasive detection of male embryos at the lay stage, even through the eggshell using lasers similar to candling. This enables efficient sexing before incubation. Other selectable genes could also be applied, combined with “null segregant” approaches already standard in plant breeding (Venkatesh et al., 2016).This strategy eliminates the wasteful “hatch-and-cull” cycle, producing only wild-type laying hens for eggs while allowing improved handling, incubation, and nutrient recovery from males. The result is improved production efficiency, higher food quality, and more ethical farming practices.

Myostatin (MSTN), a member of the TGF-superfamily, serves as a well-known negative regulator of myogenesis during skeletal muscle development by inhibiting the proliferation and differentiation of myoblasts. It is predominantly found in muscle tissues and plays a crucial role in regulating both embryonic development and the maintenance of adult tissue homeostasis (Doran et al., 2017). The absence of MSTN leads to excessive skeletal muscle growth, highlighting a significant mechanism that controls muscle size in healthy individuals. In mice lacking the myostatin gene, muscle fiber hyperplasia and hypertrophy resulted in a dramatic increase in skeletal muscle mass, producing animals approximately twice the size of their wild-type counterparts (Lee and McPherron, 2001). Successful CRISPR/Cas9-mediated gene editing to knock out the myostatin gene has been reported in sheep (Han et al., 2014) and medakafish (Yeh et al., 2017). Successful editing of the chicken MSTN gene was achieved both in vitro and in vivo using the D10A nickase variant of CRISPR/Cas9, resulting in the absence of MSTN protein expression in vitro (Lee J. H. et al., 2017) and, in vivo, chickens exhibiting increased breast and leg muscle mass along with reduced abdominal fat deposition (Kim et al., 2020). Interestingly, targeted MSTN mutagenesis resulted no detectable change in either cellular morphology (Lee H. J. et al., 2017) or body weight in knockout chickens in comparison to wild-type counterparts (Kim et al., 2020).

Egg allergy is the most common food allergy in children, affecting up to 2% of the population and being the second most common IgE-mediated food allergy in infants and young children after cow’s milk allergy (Sicherer and Sampson, 2006; Rona et al., 2007). It is estimated that between 0.5% and 2.5% of young children develop egg-specific IgE antibodies in response to egg allergens (Rona et al., 2007). A population study conducted in Australia revealed that 8.9% of infants are allergic to chicken eggs (Osborne et al., 2011). Osterballeand co-workersreported a prevalence rate of 1.7% for food allergies on their list (Osterballe et al., 2009). Ovomucoid (Gal d1), ovalbumin (Gal d2), ovotransferrin (Gal d3), lysozyme (Gal d4), and albumen (Gal d5) are the major allergenic proteins in chicken eggs, with Gal d1–d4 found in the albumen and Gal d5 in the yolk (Tan and Joshi, 2014). Additionally, the egg yolk proteins apovitellenin I and IV cause allergic reactions (Tey and Heine, 2009). Egg allergy corresponds to food allergy type I, which is distinguished by atopic dermatitis, eosinophilic esophagitis, and cell-mediated disorders. Although ovalbumin constitutes approximately 54% of egg allergens and ovomucoid is the predominant allergen (Caubet and Wang, 2011). Due to its high heat stability, resistance to proteolytic enzymes during digestion, and potent allergenicity, OVM is more difficult to eliminate than OVA (Bernhisel-Broadbent et al., 1994). Therefore, gene disruption of egg white allergen genes such as OVA and OVM has the potential to reduce allergenicity in eggs, thereby reducing immune responses in individuals who are allergic to egg white–containing foods and vaccines. By inducing PGC mutations with TALEN, Park et al. (2014) created chickens with a specific gene knockout aimed at the OVA gene. This study describes the successful generation of heterozygous OVA gene mutant offspring in which nucleotide deletion mutations of ORF shifts led to the loss of OVA gene function. This was the first study to demonstrate the efficacy of site-specific nuclease-mediated genome-editing technology in producing mutant chickens. Oishi et al. efficiently (>90%) mutagenized OVA and OVM cultured chicken PGCs using plasmids encoding Cas9, a single guide RNA, and a gene encoding drug resistance, followed by transient antibiotic selection. In their experiments, neomycin-treated cells led to more efficient mutations of these two genes (34% in OVA and 13% in OVM). By transplanting mutant-ovomucoid PGCs into recipient chicken embryos, homozygous and heterozygous mutants with OVM gene disruptions were generated. Eggs produced by hens with homozygous mutations in these allergen-encoding genes may be tolerable for those with egg white allergies. It is possible, albeit time-consuming, to cross OVA and OVM mutant chickens to produce lines with mutations in multiple allergy-related genes. Alternatively, given the efficiency of CRISPR/Cas9 mutagenesis in chicken PGCs, it may be possible to generate hens with the disruption of multiple allergenic genes more quickly by disrupting them simultaneously in PGCs. This method of manipulating the chicken genome to produce allergen-free eggs is an exciting new way to combat egg allergies and provide a healthier, safer egg-eating experience for those who are allergic to them.

Few concepts have been developed to demonstrate the potential role of CRISPR/cas9 in the production of “designer eggs”, or eggs whose biochemical composition has been modified to meet a specific need. Egg lipid content could be modified by targeting several key regulators in the form of very low-density lipoproteins (VLDL) in the ovary (Schneider, 2009). It has been reported that a chicken strain carrying a single mutation at the VLDLR locus, the “restricted ovulator,” or R/O, lays small eggs very infrequently, accounting for only about 2% of the eggs laid by wild-type hens (Elkin et al., 2006). As a result of their inability to effectively deposit VLDL and VTG into their oocytes, mutant females develop severe hyperlipidemia and atherosclerosis-like characteristics. Roosters that are VLDLR-/VLDLR+ (carriers) have a normal lipid metabolism. VLDLR females, which represent a model for an oocyte-specific receptor defect leading to familial hypercholesterolemia, are sterile due to their inability to produce eggs. Eggs with low cholesterol were produced by the increased expression of genes encoding for cholesterol 7 alpha-hydroxylase (Cyp7a1) and apolipoprotein H (ApH) during the synthesis of bile acid and cholesterol efflux. While the decreased levels of very low-density lipoprotein receptor (VLDLR), apolipoprotein B (ApoB), apovitellenin 1 (ApoVLDlII), and vitellogenin (VTGI, VTGII, and VTGIII) genes expressed in the ovary are indicative of atherosclerosis, they do not explain the disease (Zhou et al., 2014). Given its role in regulating cholesterol levels, Pcsk9 is a useful proof-of-concept, and this gene was successfully knocked out with CRISPR/Cas9, with the effects lasting for 6 months (Science Daily, 2018). Oishi et al. (2016) recently successfully (>90%) mutagenized two major egg allergens, namely ovalbumin (Gal d2) and ovomucoid (Gal d1), in cultured chicken primordial germ cells (PGCs) via transfection using plasmids encoding Cas9, a single guide RNA, and a gene encoding drug resistance, followed by transient antibiotic selection. In their experiments, neomycin-treated cells caused a more efficient mutation of these two genes (34% in OVA and 13% in OVM). By transplanting CRISPR-induced mutant-ovomucoid PGCs into recipient chicken embryos, homozygous and heterozygous OVM gene disruptions were generated. Chickens with homozygous mutations in these allergen genes produced eggs with low allergenicity, which a person with egg white allergies could tolerate.

Poultry disease outbreaks are a serious threat to the commercial poultry sector and can cause catastrophic losses for both developed and developing nations’ economies. Pandemic infections like avian influenza (AI) and avian leukosis virus (ALV) have had a significant negative impact on the poultry business and the general public. The avian influenza virus (AIV), which may quickly reassort and become hypervirulent, that can cause unforeseen pandemics with high mortality rates (Suarez and Schultz-Cherry, 2000). Depending on the age, health, and antigenic distance of the virus, the effectiveness of existing vaccination techniques, which employ live or inactivated viral vaccine strains to suppress AIV in poultry, is either restricted or non-existent (Barber et al., 2010). Therefore, the development of long-term, effective strategies to control new diseases is important and has long been a priority.

Another objective of avian CRISPR/Cas9-based genome editing technology is disease-resistant bird lines. Breeding for disease resistance presents a big challenge for the chicken industry. Although genetic variation is one of the main factors determining resistance, the practical uses in poultry have not yet been identified. We may now analyse genetic, epigenetic, and transcriptome differences within a species or closely related species to find factors linked to disease susceptibility and resistance because of the quick growth of genomic resources and next-generation sequencing. For instance, the Fayoumi chicken is renowned for being immune to several diseases. According to recent studies, the gene expression of two different genetic lines of the same species, the Leghorn and Fayoumi chickens, reacts differently to AIV infection (An et al., 2019). Breeding disease-resistant chickens may be made easier with more investigation into these differently expressed genes and the use of gene editing technology to introduce those notable genomic changes into the chicken genome. Since prior studies have indicated that overexpression of short hairpin RNA, which precisely regulates viral RNA polymerase expression, may limit AI transmission, genome editing is one of the most promising approaches for disease resistance in avian species.

The W38 site of the chNHE1 receptor is the primary binding site for ALV-J infection, and its disruption can generate resistant chicken lines. Precise, targeted disruption of tva, tvb, and chNHE1 receptor genes has been reported to enhance resistance to ALV subtypes A, B, and J by interfering with viral entry through frameshift-induced loss of receptor function. Notably, the proportion of infected DF-1 cell clones was significantly reduced in all knockout lines except tvb (Lee HJ. et al., 2019), indicating that frameshift mutations in tvb did not confer the expected level of resistance. This suggests that a more precise HDR-based editing strategy may be required to achieve full resistance. LentiCRISPR-mediated generation of W38 chNHE1 knockout PGCs resulted in markedly reduced p27 antigen titers and increased env expression following ALV-J infection compared with wild-type controls (Zhou et al., 2025). In vivo studies further demonstrated that chickens carrying this knockout exhibited enhanced resistance to ALV-J, as reflected by lower viraemia (proviral copy numbers) and reduced p27 titers (Koslová et al., 2020; Kheimar et al., 2021). Similarly, homozygous frame-shifting indels in the tva, tvc, and tvj receptors introduced premature stop codons that conferred resistance to ALV subtypes A, C, and J, respectively, in DF-1 cells (Koslová et al., 2018).

A notable example that helps illustrate disease mechanisms is the discovery of the chicken ANP32A (chANP32A) protein as a species-specific host factor required for the polymerase activity of AIV and defining a barrier to zoonotic transmission (Park Y. H. et al., 2020). They found that chicken ANP32A alone and not ANP32B and ANP32E, plays a key role in facilitating vPol activity of these viruses. Additionally, they also found that the human ANP32C, ANP32D, and ANP32E have suppressive effects on vPol activity as compared to human ANP32A and ANP32B. Building on this, Idoko-Akoh et al. (2023) applies genome editing to explicitly block AIV replication and transmission in chickens by targeting critical ANP32 family members. Their results demonstrate that while edited birds exhibit strong resistance to infection, complete protection is only achieved by ablating the entire ANP32 family, revealing the redundancy among isoforms exploited by the virus for escape and adaptation. Unlike human ANP32A (huANP32A), the chicken version contains an additional 33 amino acid segment, which significantly enhances the viral polymerase activity in avian cells (Long et al., 2019). Using gene editing technologies to replace the chANP32A gene with the huANP32A gene may lessen the AIV increased polymerase activity in chicken cells, giving the birds illness resistance.

A further intriguing route for learning and maybe identifying gene editing targets for disease resistance is the comparative genomics of chickens and ducks. Despite being related to chickens, ducks have quite distinct innate immune systems and levels of tolerance to AIV infection (Smith et al., 2009; Blyth et al., 2016). Due to their lack of the RIG-I gene, chickens have been demonstrated to be more vulnerable to AIV infection than ducks (Barber et al., 2010). It is possible to create hens with increased influenza resistance using genome editing by precisely introducing RIG-I or RIG-I-like “natural” disease-resistance genes into chicken genomic safe harbour regions. Furthermore, HIV-related mutations in the CCR5 host receptor gene have offered genetic evidence in support of this strategy. Simple in vitro and in vivo testing of altered creatures would be made possible by genome editing of these receptors; this research may aid in the creation of disease-resistant chickens. Recently, the role of T cells in chicken immunity has been elucidated through the development of T cell-knockout chickens (Heyl et al., 2023). Together, these studies significantly advance understanding and practical applications for controlling avian influenza: the mechanistic clarity informs rational gene editing strategies, and experimental genome editing demonstrates the potential and complex requirements for generating truly resistant chicken lines.

Climate change, particularly global warming, is a significant factor adversely affecting poultry livestock production and product quality. According to St-Pierre and colleagues, the poultry industry suffers an estimated annual economic loss of USD 126–165 million due to heat stress and other climate-related challenges (St-Pierre et al., 2003). Heat stress alone significantly reduces egg production and deteriorates meat quality (Wasti et al., 2020). Traditional breeding methods have struggled to keep pace with these rapidly changing environmental pressures. There is an urgent need to develop location specific climate resilient varieties which could be possible through investigation of the transcriptomic profiles of climate resilient species viz., indigenous chicken breeds and other poultry species such as ducks, quails, guinea fowl, and turkeys to explore the novel genes mediating stress mechanisms. These species are considered valuable for their innate tolerance and survival under adverse climatic conditions and disease outbreaks. Exploring the potential for silencing, up-regulating or introducing genes associated with thermo-tolerance using CRISPR/Cas9 technology offers a promising solution. These genes can potentially be introduced into more vulnerable breeds to enhance their resilience. Recent work by Rachman et al. (2024) on the genomic analysis of Nigerian indigenous chickens identified key thermo-tolerance and immune response genes, including cytochrome P450 2B4-like, TSHR, HSF1, CDC37, SFTPB, HIF3A, SLC44A2, and ILF3. Heat shock proteins (HSP70, HSP90) and thyroid hormone receptors have already been recognized as central to the thermal physiology of chickens. With the advent of CRISPR/Cas9, the expression of these heat-responsive genes can be precisely modulated, thereby enhancing the capacity of birds to maintain cellular function under heat stress.

The market value of biopharmaceuticals has been steadily increasing due to the quick advancements in biotechnology. Avian bioreactors have been explored to produce specific recombinant proteins in eggs (Zhu et al., 2005) via embryonic microinjection of retroviral or lentiviral vectors. However, these early approaches often failed to achieve heritable phenotypic gene expression in eggs, likely due to factors such as transgene silencing, ectopic expression, or insertional mutagenesis disrupting host genes. For pharmaceutical proteins to be produced inexpensively, more than 300 eggs must be laid by hens each year. There are roughly 10 major protein types found in chicken eggs, which makes it easier to separate and purify target proteins. Furthermore, medicinal compounds made from chicken eggs may be more bioactive because of the similarities and differences between the protein modifications in chicken, such as the N-glycosylation pattern, and those in humans. According to reports, transgenic chicken can generate therapeutic proteins such ß-galactosidase and ß-lactamase, interferon-a-2b, interferon-ß-1a, granulocyte-colony stimulating factor, human FSH, human erythropoietin (EPO), and human EGF. This is based on the previously described advantages (Penno et al., 2010; Park et al., 2015; Shi et al., 2020; Mukae et al., 2021; Xie et al., 2024).

In the recent times, CRISPR/Cas9 genome editing system combined with germline-competent PGCs, allowing the targeted integration and expression of exogenous genes in ovarian cells. These genes are expressed in egg whites, typically under the control of the OVA promoter, yielding 0.5–3.4 mg of protein per egg (Penno et al., 2010). Using a knock-in (KI) strategy, cDNA constructs are precisely introduced into PGCs via the CRISPR/Cas9 system to produce germline chimeric roosters. These roosters can transmit the transgene, leading to the generation of transgenic hens that lay eggs containing the protein of interest (Park et al., 2015). Notable achievements include the production of monoclonal antibodies (mAbs) in the egg white, with yields ranging from 1.4 to 1.9 mg/mL of albumen. These mAbs are among the most effective biopharmaceuticals used in treating a wide range of human diseases, including cancer, autoimmune disorders, inflammatory conditions, and infectious diseases (Mukae et al., 2021).

Recent advancements include the production of human adiponectin (ADPN), a hormone derived from adipose tissue with therapeutic potential for insulin resistance. Gene-edited chickens have been engineered to express ADPN at yields ranging from 0.59 mg to 4.59 mg per egg (Kim et al., 2023; Yoo et al., 2024). Additionally, human interferon-beta (hIFN-β), known for its antiviral and antiproliferative effects, has been produced in egg whites at concentrations of 1.9–4.4 mg (Oishi et al., 2018). Proteins used in laboratory research have also been successfully expressed in eggs of CRISPR-edited chickens, with yields between 4.96 and 9.86 mg. Enhanced Green Fluorescent Protein (EGFP) and Green Fluorescent Protein (GFP), commonly used as visual markers to validate genetic modifications, have also been produced (Harel-Markowitz et al., 2009). Altogether, the findings suggest chicken bioreactor as an efficient alternative, scalable and reliable recombinant protein production system (bioreactors) (Meng et al., 2025; Mozdziak and Petitte, 2004; Lillico et al., 2007). By combining targeted genome editing with stable germline transmission, gene edited chickens offer a promising, cost-efficient system for generating high yields of therapeutic and laboratory-grade proteins in egg whites.

In a process-based regulatory system, oversight is determined primarily by the techniques used to create the genetic modification, regardless of the final properties or traits of the edited organism. Under this approach, if genome editing technologies such as CRISPR, TALENs, or ZFNs are used—even if no foreign DNA remains in the resulting organism—the product is subject to strict genetically modified organism (GMO) regulations.

European Union: The European Court of Justice ruled in 2018 that organisms modified by mutagenesis techniques, including recent genome editing methods, fall within the scope of GMO legislation (Court of Justice of the European Union (CJEU) (2018)). As a result, any animal or plant produced using genome editing technologies is subjected to the same stringent approval, labeling, and traceability requirements as traditional GMOs, regardless of the final product’s genetic composition.

New Zealand: New Zealand maintains a highly precautionary, process-based system. The Environmental Protection Authority (EPA) classifies all organisms created or altered through modern gene-editing technologies as GMOs, demanding comprehensive regulatory approval.

Conversely, the product-based regulatory system focuses on the attributes of the final organism rather than the technologies used in its production. Regulatory scrutiny applies mainly to whether the new organism contains foreign genetic material (transgenes) or exhibits novel traits that might pose safety or ethical risks.The U.S. Food and Drug Administration (FDA) and U.S. Department of Agriculture (USDA) have adopted a product-based approach for genome-edited animals and plants. The agencies evaluate genome-edited products based on their end characteristics. If the genome-edited animal is free of transgenes—meaning it does not contain DNA from a different species, and the changes could be achieved through conventional breeding—it is generally not classified as a GMO and may be subject to less stringent regulation. However, if foreign DNA remains in the organism, the product falls under traditional GMO oversight.

Many countries in South America (e.g., Argentina, Brazil), and parts of Asia have followed the U.S. lead, adopting regulations that emphasize the final product’s attributes over the specific editing methods used. Recently, Argentinian company has produced the world’s first genome edited foals using CRISPR mediated genome editing technology. Argentina’s National Advisory Commission on Agricultural Biotechnology (CONABIA) has evaluated proposed gene edited animals that do not contain any foreign DNA or a new combination of genetic material and judged them to be exempt from GM regulation. These include gene edited applications in fish (tilapia), cattle, and horses (Fernández Ríos et al., 2025; Wray-Cahen et al., 2024). However, The International Federation of Horseracing Authorities (IFHA) and the International Federation for Equestrian Sports (FEI)3 have prohibited gene doping.

As of now, there have been no reported commercialized LM animals in South Korea; only experimental research has been announced. The current regulatory framework in the country defines terms related to genetic modification, modern biotechnology, and GMOs using criteria set in bio-safety guidelines. However, the existing regulations limit the definition to recombinant DNA, excluding comprehensive coverage of the latest new biotechnology advancements. Specifically, genetically modified animals are defined as those whose genetic material has been altered by recombinant DNA technology, encompassing modified gametes, embryos, and limited to cultured cells derived from fetal or adult organs. This implies that animals modified using advanced new biotechnology techniques like gene editing might fall outside the scope of genetically modified animals (Van Eenennaam et al., 2019; Lim and Choi, 2023; Wray-Cahen et al., 2024).

In India, as per the National Guidelines for Stem Cell Research (2017) of the Indian Council of Medical Research (ICMR), Department of Health Research (DHR) and Department of Biotechnology (DBT), Genome modification including gene editing (for example by CRISPR-Cas9 technology) of stem cells, germ-line stem cells or gamete and human embryos is restricted only to in-vitro studies. It will require thorough review by the Institute Committee for Stem Cell Research (IC-SCR), Institute Ethics Committee (IEC) and Institute Bio-Safety Committee (IBSC), and finally by Review Committee on Genetic Manipulation (RCGM). So far no permission has been granted for the release of any GE animal in commercial market.

In UK, genome-edited animals for food require ethical consideration and specific regulatory permission; however, a recent change in law in England (the Genetic Technology (Precision Breeding) Act) allows for the commercial development and sale of precision-bred food. The Nuffield Council on Bioethics emphasizes the need for strong public dialogue and clear welfare standards to guide the responsible application of this technology. According to EU law, organisms whose genomes have been modified using the CRISPR/Cas method are to be considered GMOs. Their use would therefore require a genetic engineering approval and, under current law, they could only be kept in a genetic engineering facility. Free-range husbandry would then be equivalent to a release project. Without appropriate legal adjustments, mass use would certainly be inconceivable. In the UK, genome-edited animals for food require ethical consideration and specific regulatory permission; however, a recent change in law in England (the Genetic Technology (Precision Breeding) Act) allows for the commercial development and sale of precision-bred food.

The divergence between process-based and product-based systems creates a patchwork of regulatory environments internationally. This affects global research collaborations, commercialization strategies, and consumer acceptance of genome-edited animals. For example, a genome-edited chicken line developed in the U.S. and considered non-GMO could face significant regulatory hurdles if exported to the EU. Safety and risk assessment are crucial when regulating gene-edited poultry products. The main risk is off-target effects, which could result in unintended genetic changes with unpredictable consequences (Dimitrov et al., 2016). Long-term effects on animal health and the environment must also be carefully evaluated. Some studies suggest that precise CRISPR/Cas9 editing can, for example, confer disease resistance in poultry without apparent adverse effects (Koslová et al., 2020). However, ongoing monitoring and periodic reassessment are vital to identify and mitigate risks promptly. The involvement of bio-safety and bio-security experts is equally important to address the dual-use potential of gene editing technologies.