Introduction
The improvement of meat production in the modern livestock industry is the result of efforts that have improved the growth of livestock animals by considering various factors, including but not limited to nutritional, environmental, and genetic factors. In addition to the optimization of external factors such as management and nutrition, meat production and quality traits of livestock animals have been gradually and directly improved over decades of selective breeding of individuals with desirable traits. Selective breeding, focusing on production traits, has achieved dramatic increases in the growth rate and body weight of modern farm animals, including meat-type chickens and pigs (Chen et al., 2002; Zuidhof et al., 2014). Moreover, the availability of DNA information and genetic techniques for predicting genetic values of livestock animals enables producers to predict and decide breeding strategies based on the linkage disequilibrium between quantitative trait loci and genetic markers within the genome (Meuwissen et al., 2001; Goddard et al., 2010; Meuwissen et al., 2013).
Beyond the use of DNA information, the advent and advancement of genome editing technology would allow producers to directly modify and obtain desired traits by targeting associated genes within just a couple of generations. Genome editing was first achieved using homologous recombination by introducing long DNA templates with homologous DNA sequences to induce recombination within the target sequences of the cell’s genome (Capecchi, 2005). The efficiency and on-target accuracy of genome editing were further improved with the development of site-specific nucleases (SSNs), including zinc-finger nucleases and transcription activator-like effector nucleases (Joung and Sander, 2013; Urnov et al., 2010). By engineering a DNA-cleaving nuclease with a DNA-binding domain, SSNs can bind to the target locus and induce double-strand breaks. Then, knockout of the target gene via random insertion or deletion mutations can occur during the DNA repair process known as non-homologous end joining (Gaj et al., 2013). On the other hand, another repair mechanism, called homology-directed repair, can be utilized to induce knock-in of the gene of interest to the target locus by providing a donor template. As the most recent SSN, the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system (Figure 1) has taken the genome editing field to the next level by greatly improving both efficiency and specificity (Walsh and Hochedlinger, 2013). Moreover, the CRISPR/Cas9 system can be easily and rapidly engineered by replacing the sequence of the guide RNA, which acts as the DNA-binding domain.
Such improvements in the efficiency and specificity of genome editing, along with the convenience in constructing and using the CRISPR/Cas9 system, have accelerated genome editing-related research and applications across diverse fields, including the livestock industry. It is not a simple task to completely regulate growth and other economically important traits of meat-producing animals with several key genes, because those traits are complex polygenic traits influenced by multiple genes. Nevertheless, understanding and discovering genes related to these traits is an important stepping stone to improving economically important traits of meat-producing animals via regulating genetic factors. For these reasons, various genome-edited farm animal models are actively being generated and investigated for potential industrial applications in animal production, health, and welfare (Lamas-Toranzo et al., 2017) by targeting genes associated with muscle growth for improving meat production (Kim et al., 2020; Li et al., 2020) and infectious diseases for improving health and welfare (Whitworth et al., 2016; Idoko-Akoh et al., 2023). Moreover, direct application of genome editing in the generation of superior lines of farm animals has gained more attention as more countries approve genome-edited animals for human consumption. Since the first approval of genetically engineered salmon for human consumption in Canada in May 2016, which produce growth hormone continually and grow bigger and faster (Waltz, 2017), Japan has also approved 2 genome-edited fish targeting leptin receptors and myostatin in October and November 2021, respectively, for increasing body weight (News in Brief, 2022a). Moreover, the recent approval of genome-edited swine without allergic proteins, called Galsafe pigs in December 2020 (Reardon, 2022), and cattle with short hair, called prolactin receptor-SLICK cattle in March 2022 (News in Brief, 2022b), further emphasizes the growing importance of genome editing in meat-producing animals.
While genome editing has rapidly advanced across various fields of animal biotechnology, there remains a notable gap in the literature regarding its specific application to meat production and quality traits. To date, no comprehensive reviews have been published that focus exclusively on the feasibility, recent technological developments, and targeted gene modifications aimed at improving meat-related characteristics in livestock. Furthermore, there is limited information available on how genome editing technologies intersect with specific traits such as muscle growth, fat composition, and other meat quality attributes. This review aims to address this gap by synthesizing current progress in genome-edited livestock models, identifying promising candidate genes for meat trait enhancement, and discussing the major scientific, regulatory, and societal challenges that must be addressed to enable broader adoption of these technologies. By providing a focused overview, this review contributes a timely resource for researchers, policymakers, and industry stakeholders interested in the future of meat production through genome editing.
Genome Editing of Myostatin for Meat Production
Muscle growth
Myostatin (MSTN) functions as a negative regulator of muscle development in animals (Chen et al., 2021). MSTN inhibits the proliferation and differentiation of myogenic precursor cells by binding to Activin receptor II-B, which decreases myogenesis and protein synthesis while increasing protein degradation (Chen et al., 2021; Lee et al., 2001). It has been consistently reported that CRISPR-mediated MSTN knockout enhances muscle growth in various livestock species (Table 1). MSTN knockout cattle showed increased muscle mass by hypertrophy, increased myofiber diameter (Zhao et al., 2022). Likewise, MSTN knockout induced hypertrophy in goats and sheep, which led to increased muscle mass. In MSTN knockout chickens, rabbits, and pigs, the increase in muscle mass is attributed to both hyperplasia (increased number of muscle fibers) and hypertrophy (increased fiber size) (Kim et al., 2020; Li et al., 2020; Lv et al., 2016; Zheng et al., 2022). However, some studies have reported that muscle growth in pigs resulted solely from hyperplasia, without a significant increase in myofiber size (Bi et al., 2016; Zhu et al., 2020), as also observed in MSTN knockout quail (Lee et al., 2020). The hyperplastic and/or hypertrophic muscle growth observed following MSTN knockout may result from differences in species, breed, gene-editing site, age, or gender. However, despite the differences, studies have unequivocally shown an increase in muscle mass.
CRISPR/Cas9-mediated genome editing in a cell.
Currently reported whole-body genome-edited animal models targeting the MSTN gene related to meat production.
| Speciesa | Methodb | Genome Editing Approach | Target Traits |
|---|---|---|---|
| Mammalian livestock | |||
| Cattle | SCNT | 6 and 115 nucleotide deletions for each allele by CRISPR/Cas9 | Hypertrophy, Muscle mass, Fat, Body weight, Meat quality (Zhao et al., 2022) |
| Goat | Microinjection into zygotes | Nucleotide deletion by CRISPR/Cas9 | Hypertrophy, Body weight (Wang et al., 2018) |
| Pig | SCNT | 6-nucleotide deletion in one allele by CRISPR/Cas9 | Hyperplasia, Muscle mass (Li et al., 2020) |
| Pig | SCNT | A nucleotide insertion by CRISPR/Cas9 | Hyperplasia, Body weight (Zhu et al., 2020) |
| Pig | SCNT | 138 nucleotide deletion by CRISPR/Cas9 | Hypertrophy, Hyperplasia, Fat, Body weight (Bi et al., 2016) |
| Rabbit | Microinjection into zygotes | A nucleotide insertion by CRISPR/Cas9 | Hypertrophy, Hyperplasia, Muscle mass, Body weight (Lv et al., 2022) |
| Rabbit | SCNT | 138 nucleotide deletion by CRISPR/Cas9 | Hypertrophy, Hyperplasia, Muscle mass, Body weight (Zheng et al., 2022) |
| Sheep | Microinjection into zygotes | Nucleotide insertion and deletion by CRISPR/Cas9 | Hypertrophy, Body weight (Guo et al. 2023) |
| Sheep | Microinjection into zygotes | 20-nucleotide deletion by CRISPR/Cas9 | Muscle mass, Body weight (Crispo et al., 2015) |
| Sheep | Microinjection into zygotes | Nucleotide deletion by CRISPR/Cas9 | Hypertrophy, Muscle mass, Body weight, Meat quality (Zhou et al. 2022) |
| Poultry | |||
| Chicken | PGC-mediated genome editing | 14 nucleotides deletion mutation & multiple indel mutations by D10A-Cas9 | Hypertrophy, Hyperplasia, Muscle mass, Fat (Kim et al. 2020) |
| Duck | Adenovirus-mediated genome editing | A nucleotide insertion by CRISPR/Cas9 | N/A (Lee et al., 2022) |
| Quail | Adenovirus-mediated genome editing | 3-nucleotide deletion mutation by CRISPR/Cas9 | Hyperplasia, Fat, Body weight (Lee et al., 2020); Fat and Feed efficiency (Lee et al., 2021); Meat quality (Kim et al. 2023) |
Investigated animals are categorized as mammals and poultry and listed in alphabetical order.
SCNT, somatic cell nuclear transfer; PGC, primordial germ cells.
In livestock, the composition of Type IIB fibers is known to contribute to muscle growth. For example, compared with random bred control (RBC) Japanese quails, heavy weight (HW) Japanese quails exhibit a greater percentage of Type IIB fibers, along with increased body weight and pectoralis major muscle mass (Choi et al., 2013). MSTN also regulates the composition of muscle fiber types. In pigs, MSTN knockout elevated Type IIB fiber composition and displayed significantly greater total muscle mass compared to wild-type (WT) pigs (Qian et al., 2022). In gene-edited chickens, MSTN knockout led to decreased Type I fibers and increased Type II fibers (Kim et al., 2020). In gene-edited quail, MSTN knockout resulted in lower Type IIA and higher Type IIB percentages (Kim et al., 2023). Although previous studies with MSTN knockout mice suggest that regulation of MEF2C and MyoD could contribute to fiber-type change, further studies need to address the mechanism of conversion of myofiber types in livestock, including avians (Hennebry et al., 2009).
Adipose growth
In addition to its role in muscle development, MSTN influences adipose tissue accumulation. MSTN promotes adipogenic differentiation by upregulating PPARγ in adipose-derived stem cells (Zhang et al., 2015a). Hence, MSTN knockout may reduce fat accumulation by shifting preadipocyte differentiation away from the adipogenic lineage, thereby limiting adipose tissue development.
Several studies have reported a significant reduction in fat deposition following MSTN knockout. In MSTN knockout cattle and pigs, carcass evaluation indicated decreased backfat thickness (Casas et al., 2004; Bi et al., 2016). MSTN knockout chickens exhibited a visible reduction in abdominal fat (Kim et al., 2020). In quail, leg and abdominal fat pad weights were significantly decreased in MSTN mutants (Lee et al., 2020). These studies consistently suggest that MSTN editing contributes to a reduction in fat accumulation across species.
Carcass productivity and feed efficiency
MSTN knockout has also been associated with growth performance, an economic trait in the livestock industry. In cattle, natural MSTN mutations increase hindquarter weight and overall carcass yield compared to WT (Gill et al., 2013). Similarly, MSTN knockout sheep and goats had higher body weights during early development (Crispo et al., 2015; Wang et al., 2018). In rabbits, edited individuals showed significantly greater body weights at 180 days of age. Among the reported species, feed efficiency was evaluated only in quail. MSTN knockout quail exhibited a significantly lower feed conversion ratio, indicating improved feed efficiency (Lee et al., 2021).
As previously described, MSTN knockout decreases fat deposition and increases muscle accretion. The biosynthesis of fat requires more energy compared to that of protein, and adipose tissue contains a higher energy density compared to muscle (Whittemore and Kyriazakis, 2006). Therefore, MSTN knockout may offer economic advantages by both enhanced growth and improved feed efficiency in livestock production.
Meat quality
In addition to growth traits and feed efficiency, meat quality is an economically important trait in meat production. Although MSTN knockout enhances lean yield, it has the potential to affect meat quality factors such as tenderness, juiciness, and marbling, which are largely influenced by intramuscular fat content. Therefore, the reduction of intramuscular fat in meat caused by MSTN knockout may raise concerns regarding flavor and texture, key factors in consumer preference. Hence, the potential impact of MSTN mutations on meat quality traits should be considered.
In both quail and sheep, MSTN mutant lines showed no significant differences in major meat quality parameters compared to WT (Kim et al., 2023; Zhou et al., 2022). These findings suggest that MSTN knockout can improve carcass composition while maintaining meat quality parameters, including pH and water-holding capacity in quail and sheep. In Belgian Blue cattle, which carry a natural MSTN mutation, increased lean meat yield and decreased marbling have been reported (Fiems, 2012). The low intramuscular fat content may result in meat that lacks the flavor and juiciness preferred by consumers. Such quality concerns may be addressed through nutritional strategies, such as dietary supplementation with unsaturated fatty acids or energy-dense feeds during the finishing period, which can enhance marbling while maintaining increased lean yield (Duckett, 2000; Kang et al., 2022). Therefore, even in ruminant models, the application of MSTN knockout could serve as a promising strategy to produce economically efficient meat without compromising overall quality.
Although MSTN knockout promotes muscle development, it may negatively impact meat quality by altering the proportion of muscle fiber types. MSTN knockout chickens exhibit increased breast and leg muscle weights but a reduced number of Type I fibers in the Biceps femoris muscle (Kim et al., 2020). Similarly, MSTN mutant Japanese quail show a lower proportion of Type IIA fibers and a higher proportion of Type IIB fibers in the deep region of the breast muscle (Kim et al., 2023). Type IIB fibers, characterized by high glycogen content and elevated ATPase activity, undergo rapid postmortem glycolysis, leading to decreased pH and reduced water-holding capacity (Mo et al., 2023). Furthermore, due to their larger cross-sectional area and lower phospholipid content, Type IIB fibers are associated with reduced tenderness and diminished meat flavor (Mo et al., 2023). However, the direct evaluation of meat flavor alterations caused by MSTN knockout remains challenging, as the MSTN gene-edited animals have not been approved for human consumption in the U.S. These legal restrictions hinder the ability to conduct consumer taste panels or market-based flavor testing. Thus, it is necessary to assess meat quality using artificial sensory systems, which can objectively evaluate texture and flavor-related attributes without human tasting (Bai et al., 2023). Although such animals are not yet legally approved for consumption in many countries, ongoing research is essential to prepare for future regulatory changes, support safety evaluation, and ensure responsible application when approval becomes viable.
Potential negative impacts and limitations
While MSTN gene editing offers clear benefits for muscle growth and fat reduction, several studies have reported unintended side effects that warrant careful consideration. One of the most documented concerns is increased calving difficulty in MSTN mutant cattle, especially in homozygous double-muscled breeds such as Belgian Blue and Piedmontese (Casas et al., 1999; Mota et al., 2017). These animals exhibit higher rates of dystocia due to increased body weight with excessive muscle mass in offspring (Fiems, 2012).
Beyond reproduction, MSTN deficiency has been associated with altered endocrine functions and reproductive traits. In cattle, delayed puberty and reduced colostrum production have been observed in MSTN mutants (Cushman et al., 2015; Arthur et al., 1988), suggesting potential disruption of hormonal balance and reproductive efficiency. Similarly, in Japanese quail, MSTN homozygous mutants exhibited a delayed onset of egg laying by approximately 5 days compared to WT birds (Lee et al., 2021). In rabbits, MSTN +/- has been associated with enlarged tongues (Lv et al., 2016). Taken together, these findings emphasize the need for comprehensive phenotypic evaluations and long-term studies on genome-edited animals, along with cautious interpretation of results across species. While MSTN editing remains a powerful tool, it must be applied with a comprehensive understanding of its potential drawbacks and biological complexity.
Modulation of myostatin signaling by its regulatory factors
The biological activity of MSTN is tightly regulated by a network of extracellular and intracellular modulators that control its bioavailability and downstream signaling. Among these, follistatin, GASP-1 (growth and differentiation factor-associated serum protein-1), and decorin are well-characterized extracellular antagonists that bind MSTN and inhibit its interaction with ActRIIB. This antagonism prevents activation of the SMAD2/3 signaling cascade, thereby promoting muscle growth. Intracellular regulators such as SMAD7 serve as feedback inhibitors, attenuating the transcriptional effects of MSTN signaling. Gene editing and genetic knockout strategies have also targeted these MSTN regulators.
For example, mice lacking follistatin exhibit reduced muscle mass, impaired regeneration, and a shift toward oxidative fiber types, and these effects are partially retained even in MSTN-null mice, indicating that follistatin regulates additional transforming growth factor-β ligands such as Activin A (Lee et al., 2010). Similarly, Gasp1-/- and Gasp2-/- mice show muscle atrophy, fiber-type switching, and regenerative defects, confirming the essential in vivo role of these antagonists in modulating MSTN and GDF-11 activity (Lee and Lee, 2013). Conversely, adenovirus-mediated expression of follistatin in mouse leg muscle significantly increased muscle mass with enhanced protein synthesis (Nissinen et al., 2021). In addition, transgenic mice with GASP-2 overexpression displayed marked muscle hypertrophy with a change from slow- to fast-twitch myofibers (Parenté et al., 2020). Taken together, these studies highlight the critical balance maintained by MSTN regulators and demonstrate that modulating their expression can profoundly influence muscle mass.
Potential Target Genes for Genome Editing in Animal Production
The growth hormone axis as a target for genetic enhancement in livestock
The growth hormone (GH) axis regulates growth, metabolism, and body composition in livestock like chickens, cattle, pigs, and sheep (Dawson et al., 1998; Lee et al., 1994; Lee et al., 2000; Pell et al., 1990; Scanes et al., 1984). It involves growth hormone-releasing hormone (GHRH) from the hypothalamus, GH from the pituitary, and IGF-1 from the liver, which mediates GH’s growth-promoting effects. Somatostatin (SST) suppresses GH release as a part of a negative feedback loop. GH boosts bone growth, muscle development, and fat mobilization, improving growth rate, carcass yield, and feed conversion efficiency, all crucial in commercial meat production (Etherton and Bauman, 1998). Enhancing GH activity has long been a target in animal breeding and biotechnology.
CRISPR/Cas9 technology enables precise targeting of the GH axis, offering new opportunities to enhance growth performance and feed efficiency through genome editing. One conceptual approach involves disrupting endogenous inhibitors such as SST or its receptors (SSTR2, SSTR5) to boost GH secretion and downstream IGF-1 activity (Murray et al., 2004; Weckbecker et al., 2003). Although potential physiological or unintended effects of complete gene knockouts must be thoroughly evaluated, these targets offer considerable potential for modulating growth-regulating pathways. In poultry, natural variation in expression levels of GH axis genes helps explain differences in growth between fast- and slow-growing breeds (El-Attrouny et al., 2021; Jia et al., 2018), highlighting the axis’s role in shaping production traits and informing the strategic selection of CRISPR targets.
Expanding genomic resources, including Single nucleotide polymorphism (SNP), data and Genome-wide association study (GWAS) findings, continue to identify candidate genes within the GH axis, such as GH, GHRH, GHR, SST, SSTR, and IGF1 that may carry breed-specific polymorphisms associated with performance traits. Critical SNPs that enhance the activity or expression of GH, GHRH, GHR, and IGF1, or reduce the activity or expression of SST and its receptors, will first need to be identified to inform precise editing strategies. Relevant regulatory regions such as promoters, enhancers, and untranslated regions can be identified using bioinformatic tools that incorporate data on chromatin accessibility, evolutionary conservation, and predicted transcription factor binding sites. The functional significance of these candidate regions can then be evaluated through functional genomics approaches, including expression quantitative trait locus (eQTL) analysis and CRISPR-based assays (e.g., CRISPRi, CRISPRa, or base editing), to determine their effects on gene expression and phenotypic outcomes.
Rather than relying on full gene knockouts, advanced genome editing technologies like base editing (Gaudelli et al., 2017) allow for precise modification of regulatory regions, such as promoters, enhancers, or the introduction of specific point mutations. Editing these regulatory regions offers a lower-risk, breed-specific strategy to fine-tune gene expression. Collectively, these approaches support the discovery and functional validation of regulatory components that can be precisely edited to enhance growth, paving the way for the development of genetically optimized poultry lines tailored to specific breeding goals.
Fat deposition in adipose and muscle tissues as a target for genetic enhancement in livestock production and meat quality
Increasing marbling while reducing subcutaneous fat offers significant benefits for meat quality, economic value, and production efficiency. Marbling enhances tenderness, juiciness, flavor, and overall palatability, making it highly desirable in premium markets such as the United States Department of Agriculture Prime. In contrast, excess subcutaneous fat lowers carcass yield, increases processing and trimming losses, and is less appealing to consumers seeking leaner cuts. Economically, higher marbling boosts meat prices and producer income without increasing carcass weight, while reducing external fat improves feed efficiency and minimizes waste. These traits can be selectively targeted by using gene-editing technologies to precisely manipulate fat deposition for long-term genetic improvement.
Gene-editing offers a powerful tool to modulate lipid metabolism in meat-producing animals by targeting key regulators of fat storage and mobilization. Adipose triglyceride lipase (ATGL) initiates lipolysis by hydrolyzing triglycerides into free fatty acids, making it central to fat breakdown (Deiuliis et al., 2008; Deiuliis et al., 2010; Lee et al., 2009; Serr et al., 2011; Zimmermann et al., 2004). Its activity is naturally inhibited by G0S2, which has been shown to suppress lipolysis in feed-restricted quail, while G0S2 disruption in chickens significantly reduced abdominal fat (Ahn et al., 2013a; Ahn et al., 2013b; Oh et al., 2011; Park et al., 2018; Shin et al., 2014). Targeted gene-editing of G0S2 in subcutaneous adipose tissue could enhance lipolysis and reduce undesirable fat accumulation.
CGI-58 (also known as ABHD5), a coactivator of ATGL, is essential for its full function (Lass et al., 2006; Li et al., 2012; Serr et al., 2011). Tissue-specific modulation of CGI-58 could redirect lipid mobilization away from subcutaneous fat and toward intramuscular depots, improving marbling. Gene-editing strategies such as ATGL or CGI-58 knockout in muscle tissue and G0S2 knockout in adipose tissue represent precise approaches to optimize fat distribution. Together, editing ATGL, G0S2, and CGI-58 enables a comprehensive strategy to reduce waste fat, improve carcass composition, and enhance desirable meat quality traits such as marbling.
Ethical, Regulatory, and Consumer Acceptance Challenges
While differences exist in the regulation of gene-edited livestock among countries, there are also many countries that show similarities in their regulation. The criteria of what should be labelled as a genetically modified organism (GMO), and therefore be subject to regulation, is one such difference that varies by country, although many countries agree on their classifications. The European Union (EU), for example, considers any mutagenesis-modified organism as a GMO regardless of how the gene has changed, making it one of the stricter countries in terms of GMO classification (Lim and Choi, 2023). The U.S. is another country with more stringent regulations. While the use of the term GMO is not present in US regulation, they instead subject all gene-edited animals, regardless of how they are modified, to regulatory approval. Oversight is provided by 3 different government agencies: the Food and Drug Administration (FDA), the Environmental Protection Agency (EPA), and the Department of Agriculture (USDA), depending on the intended use of the animals (Lim and Choi, 2023). This is not the same for countries such as Brazil, which have more lenient classifications of GMOs, exempting any mutations that exclude recombinant DNA/RNA, and edits that can be obtained through traditional breeding or natural mutation (Lim and Choi, 2023). Similar classification is seen in many other countries, including Japan, Australia, Argentina, and Colombia. These countries do not classify animals as GMOs when no foreign DNA is present, allowing gene-edited animals with edits such as knockout mutations to be regulated the same as animals produced from conventional breeding (Ledesma and Van Eenennaam, 2024). This lenient regulation of gene-edited animals is a growing trend internationally and will likely be adopted by more countries in the future (Lim and Choi, 2023).
Safety or risk assessments of genome-edited livestock represent another regulatory area that is becoming increasingly consistent across countries (Van Eenennaam et al., 2019; Kumar and Kues, 2023; Wray-Cahen et al., 2024; Li et al., 2025). While there are still some differences between countries, what is assessed is largely the same (Kumar and Kues, 2023; Ledesma and Van Eenennaam, 2024; Wray-Cahen et al., 2024). In terms of the animal’s health, these assessments tend to include immunogenicity of genome-edited animals, unintended genetic impacts, and other biological consequences. Evaluations related to the safety of food or other animal products, as well as the genome-edited animal’s potential impacts on the environment, include allergenic potential of animal products as well as toxicity, animal contamination levels, and subsequent environmental impacts (Ormandy et al., 2011; Lim and Choi, 2023). In the FDA-approved case of the commercial production of PRRS-resistant pigs, the use of gene-edited × wild-type F1 pigs may help alleviate public concerns about extensive genetic intervention (Whitworth et al., 2016; Burger et al., 2024). This approach leads to dilution of off-target mutations over generations and contributes to improved animal welfare, a more sustainable and reliable pork supply, and safer production with reduced antibiotic use and cleaner meat. These assessments and the growing global alignment in how they regulate genome-edited livestock will ensure the safety of not only the public and the environment but also the animals themselves.
There are a few ethical concerns when it comes to genome-edited livestock. One such concern is the occurrence of off-target mutations in the edited animals. CRISPR-Cas9-induced off-target mutations can disrupt gene function or introduce unexpected genomic changes, potentially leading to cancer-related processes and negative effects on animal health, especially when occurring in coding regions (Naeem et al., 2020; Shi et al., 2025). However, such mutations are rarely reported in CRISPR/Cas9 animal models (Iyer et al., 2015; Zhu et al., 2016), possibly due to controlled Cas9 delivery, selective breeding of on-target founders, and the frequent localization of off-target sites in noncoding regions. Public skepticism toward genome-edited livestock partly stems from a lack of trust in researchers and regulators (Ishii and Araki, 2016), which is further compounded by the limited use of genome-wide, high-resolution, and unbiased methods for detecting off-target effects. Therefore, more rigorous analysis at the whole-animal level is essential to improve transparency and credibility in future research.
Although genome editing technologies like CRISPR-Cas9 offer greater precision than traditional GMOs, technical challenges such as off-target mutations and mosaicism still remain and must be addressed to improve the food safety of gene-edited products (Ahmad et al., 2023). Gene-edited products generally do not contain foreign DNA or proteins, unlike GMOs. As a result, they often do not leave detectable residues of the editing process in the final product, especially when no transgene is used (Ahmad et al., 2023). Researchers are developing strategies to optimize editing conditions and detect unexpected changes through advanced genomic analysis (Modrzejewski et al., 2020). Ethically beneficial applications, such as producing hornless cattle to eliminate dehorning, demonstrate the potential for improving animal welfare and public perception (Yunes et al., 2021). This distinction matters for regulatory decisions, consumer acceptance, and ethical debates around modern biotechnology.
However, the adoption of CRISPR technology in food production will largely depend on public acceptance and its perceived value. (Shew et al., 2018; Subica, 2023; Bearth et al., 2024). Practical adoption requires transparent regulation and trust-building (Hallerman et al., 2024). For example, the UK categorizes genome-edited plants and animals as “Precision Bred Organisms,” signaling a shift toward tailored governance frameworks (Coe and Ares, 2023). Ultimately, enhancing technical accuracy, ensuring ethical treatment of animals, and maintaining regulatory transparency are critical to achieving societal acceptance and realizing the potential of genome editing in livestock. Scientists should actively engage with the public to clearly communicate the benefits, risks, and regulatory distinctions of genome-edited livestock. Transparent communication and addressing concerns about safety, ethics, and animal welfare are essential for building consumer trust. Science-based public education and outreach play a key role in enhancing awareness and acceptance of gene-editing technologies (Kuo et al., 2024). In future research, advanced and rigorous methods such as qPCR, digenome-seq, and whole-genome analysis will be necessary to identify unintended edits, residual proteins, or off-target effects, ensuring precise detection of genetic alterations at the animal level (Zhang et al., 2015b; Martin et al., 2016; Modrzejewski et al., 2020).
Conclusion
Genome editing technologies, particularly targeting the MSTN gene, have shown strong potential to enhance muscle growth, reduce fat accumulation, and improve feed efficiency in livestock. These advancements present promising avenues for increasing meat production and economic returns across multiple species. Additionally, other candidate genes involved in growth regulation and fat metabolism provide further opportunities for precision genetic improvements. However, to fully realize the benefits of genome-edited animals, ongoing challenges such as ethical considerations, regulatory approval, and public acceptance must be addressed.With continued innovation in editing tools and the development of transparent regulatory frameworks, genome editing is poised to play a transformative role in the future of animal agriculture.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
This research was supported by the United States Department of Agriculture National Institute of Food and Agriculture Grant (Project No. 2022-67015-36482).
Author Contribution
Wonjun Choi: Writing - original draft; Joonbum Lee: Writing - original draft; Su Hyun An: Writing - original draft; Michelle Wright: Writing - original draft; Zhijie Deng: Writing - original draft; Kichoon Lee: Conceptualization, Supervision, Funding acquisition, Writing –review & editing.
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