A new era of genetics dawned in the 2010s with the discovery of the revolutionary CRISPR/Cas technology, which enables the targeting and editing of specific genes or genomic loci with high precision [4]. Since then, CRISPR-Cas has become a household name, as it has quite literally democratized genome editing across the globe due to its versatility, flexibility, high efficiency, and relative ease of adoption in diverse biological systems. Conventional CRISPR-Cas9 and advanced tools like base editors and prime editors have become principal tools for disrupting gene functions, replacing alleles, creating precise insertions or deletions, and conducting large-scale chromosome engineering [17]. The delivery of CRISPR reagents to specific cell types and their encapsulation within cargo vehicles pose significant challenges. Furthermore, the regeneration of edited plants remains problematic in many recalcitrant crops. Addressing the efficiency of editing in polyploid crops necessitates dedicated attention.

Fascinatingly, ongoing public discourse has prompted many countries worldwide, including India, to treat transgene-free genome-edited plants similarly to conventionally bred varieties, leading to the formulation of legal regulatory guidelines. Encouraged by the favorable atmosphere surrounding genome editing, rapid technological advancements have already borne fruit in the form of commercialized genome-edited crops and therapeutics aimed at curing genetic diseases. High oleic soybean, high GABA tomato, waxy corn, pungency-free mustard green, fast-growing red sea bream, and tiger puffer fish have been developed through genome editing and have already been marketed in the USA and Japan. Additionally, CRISPR-Cas9 made history in the field of therapeutics when the UK granted the world's first-ever approval to a CRISPR therapy, Casgevy, for treating sickle cell anemia and β-thalassemia in November 2023. Shortly thereafter, the USA followed suit and approved clinical use of the same therapy in the country. Numerous gene editing therapies are at different stages of clinical trials and are poised to reach the clinic soon.

Given the unprecedented technological advancements in genome editing, and their rapid translation for human welfare, we decided to put forward the idea of this thematic special issue on “Genome Editing for Food, Nutrition, and Health: From Basic Biology to Translational Research”. This special issue showcases recent exciting developments and applications across various organisms including microbes, insects, plants, and mammals,  while shedding light on existing challenges and emerging solutions.

Base editing, one of the major advances in the genome editing field, enables the targeted alteration of one type of DNA base to another within the genomes of diverse organisms, holding great promise in biotechnology, agriculture, and therapeutics [16]. Shelake and Kim [19] expanded the base editing toolbox for bacterial genome manipulation by develo** multiple base editors with Cas9 variants. The authors successfully extended the base editing activity window by utilizing the circularly permuted Cas9 (CP-Cas9) variant and expanded targetability beyond the NGG PAM by employing the SaCas9-KKH variant. Interestingly, both cytosine base editor (CBE) and adenine base editor (ABE) have been developed with the two Cas variants. The authors utilized SaKKH-CBE for random mutagenesis of the rpoB locus to evolve rifampicin resistance in bacteria. This comprehensive study has generated multiple base editing tools applicable for editing the bacterial genome, enabling versatile applications.

Insects constitute the largest group in the animal kingdom, encompassing both beneficial organisms and destructive pests. Among them, the common fruit fly, Drosophila melanogaster, stands as an extensively utilized genetic model, often hailed as the 'Queen of Genetics.' Genome editing has introduced unprecedented convenience and versatility to gene function studies, not only within model insects but also in agricultural pests. In this special issue, Karuppannasamy and Wishard et al. [12] showcased Cas9 RNP-mediated genome editing in the mango fruit fly, Bactrocera dorsalis, and studied how G0 heterozygous edits contribute to the white eye phenotype. The insights gleaned from this study hold promise for elucidating the loss of function in genes pertinent to sex determination, spermatogenesis, chemoreception, oogenesis, and other pivotal biological traits in insects.

Successful implementation and realizing the full potential of CRISPR-Cas technology in agriculture face hurdles, including scientific, legal, and societal factors. Ghosal [8] provides a succinct overview of the entire scenario, from concept development and invention to regulation and the roles of various stakeholders, for individuals from diverse spheres of society. Public perception and understanding play crucial roles in the acceptance and deployment of CRISPR-edited crops, necessitating widespread education across society for their adoption.

In their review, Singh et al. [20] provide a concise overview of both conventional CRISPR-Cas and advanced technologies, discussing various domains of their application such as abiotic stress tolerance, biotic stress resistance, and quality improvement. Additionally, the authors devote a significant portion of the review to highlighting current technical challenges in editing experiments and recent developments aimed at addressing these challenges.

Crop yield and productivity rely heavily on nitrogen fertilization. However, due to the inefficient use of applied nitrogen by crops, residual nitrogen causes numerous detrimental effects on the environment. Therefore, enhancing nitrogen use efficiency (NUE) in crops is crucial for sustainable agriculture. Kumar A. et al. [14] assessed the past and present state of knowledge on identified genes related to NUE and synthesized how they could be manipulated with existing genome editing tools to improve NUE in crops. The authors discussed factors involved in nitrogen uptake, translocation, assimilation, and remobilization, providing strategies to enhance NUE.

Although genome editing has been extensively used in major crops such as rice, wheat, and maize, numerous bottlenecks hinder its efficient application in minor or orphan crops. Unless these obstacles are addressed, the utilization of this technology to enhance minor crops will be impeded, resulting in slow adoption and hindering global efforts to diversify agriculture. In this special issue, several groups addressed crop-specific challenges by reviewing the current state of knowledge, providing up-to-date status, and listing potential target genes for editing. Sapara et al. [18] extensively reviewed the case of millets, Kumar R. et al. [15] presented a concise review of cotton genome editing, and Singh et al. [21] focused on peanut genome editing. One of the major bottlenecks is the delivery of CRISPR reagents and regeneration of the edited cells. Focusing on recalcitrant oilseeds and millets, Ghosh [7] reviewed emerging plant transformation methods and strategies for improving regeneration, and discussed potential ways to address the existing limitations in delivery.

One of the attractive features of CRISPR-Cas technology is its flexibility in using a guide RNA library to conduct large-scale screening for functional genomics. The article by Dutta et al. [6] focuses on reviewing examples of CRISPR screening in plants and discusses the future direction of using CRISPR gRNA libraries for directed evolution of target loci by generating novel genetic variations. The authors present strategies for screening and validating mutant populations through phenotype-genotype correlation, as well as provide a comparative account of different delivery methods for guide RNA libraries.

The epigenome comprises the complete set of chemical modifications to DNA (e.g., methylation) and histone proteins (e.g., acetylation), which have the capacity to alter gene expression. Deactivated Cas9 (dCas9) has been fused with effector proteins to develop various classes of epigenome editors capable of modifying the epigenetic status of a target genomic region. In a minireview, Subramanian et al. [22] present a concise overview of strategies to modulate the epigenome in plants by writing or erasing chemical modifications of DNA and histones.

In the realm of healthcare, genome editing emerges as a promising avenue for tackling cardiovascular disorders, as highlighted in one of the articles of this special issue. Duddu et al. [5] reviewed and proposed strategies aimed at precisely targeting genetic mutations associated with both inherited and acquired cardiovascular diseases. By doing so, researchers aim to mitigate disease severity, improve heart function, and pave the way for personalized therapeutic interventions.

Asrar et al. [2] reviewed CRISPR-Cas9-based therapies for breast cancer exemplifying the potential of genome editing in revolutionizing cancer treatment. Through targeted modifications of crucial genes implicated in tumor progression and therapy resistance, researchers envision novel therapeutic strategies with enhanced efficacy and precision.

Jaiswal et al. [10] discuss the implications of the discovery of Anti-CRISPR (Acr) proteins in phages. Acrs are small proteins found in phages that act as defense molecules against CRISPR-Cas bacterial immune system. Acrs can be used to create controlled and reversible CRISPR-Cas-mediated systems, thereby unlocking opportunities for genome editing with greater precision. The review further discusses how Acrs may be utilized to decrease off-target effects of CRISPR-Cas technology and thus enhance their potential as tools for genome editing.

The year 2019 witnessed the discovery of another major tool in the field of genome editing called “prime-editing” [1]. This technique can edit genes without the need for making double-stranded breaks. It can be utilized to make precise edits such as insertions, deletions, base substitutions, and combinations thereof at target gene sites. Das (2024) discusses the application of prime editing in beta-hemoglobinopathies, thereby highlighting its transformative potential in monogenic disorders [3].

This special issue also presents two commentary articles from experts. Michael Halewood [9] comments on the dynamics of emerging rules for sharing benefits arising from the use of digital sequence information (DSI). This article presents up-to-date status and arguments about the negotiations that are underway around DSI, particularly for researchers engaged in using genomic resources or the sequence data for product development through recently developed new breeding technologies like genome editing.

Rapid and accurate diagnosis is crucial for effective disease management. The high levels of nucleic acid specificity of Cas proteins have been utilized to develop nucleic acid-based diagnostic tools. In their commentary, Kasfy et al. [13] discuss the suitability of CRISPR-based diagnostic methods as point-of-care diagnostics and highlight the challenges that need to be overcome to make them field-deployable.

We believe the Special volume will serve as a valuable resource for researchers to utilize the CRISPR system for basic discovery, as well as translational research to accelerate crop improvement for climate resilience and sustainable agriculture, and to discover innovative solutions for enhancing human health. We express our gratitude to the authors for their contributions to the journal. We are thankful to Prof. Rajeev Kumar Varshney of Murdoch University for writing the foreword for this special issue. Additionally, we extend our appreciation to the reviewers for their timely support in completing the special issue.