CRISPR technology has revolutionized gene editing, with recent studies highlighting its applications and advancements. One significant study demonstrated the efficacy of CRISPR-Cas9 gene editing combined with Nexiguran Ziclumeran for treating ATTR cardiomyopathy, achieving a mean percent change of -89% in serum TTR levels at 28 days and -90% at 12 months (ref: Fontana doi.org/10.1056/NEJMoa2412309/). Another innovative approach, MultiPerturb-seq, integrates single-nucleus chromatin accessibility and transcriptome profiling, allowing for the identification of differentiation genes in pediatric cancers, establishing ZNHIT1 as a potential therapeutic target (ref: Yan doi.org/10.1038/s41587-024-02475-x/). Furthermore, saturation profiling using prime editing has characterized 2,476 single nucleotide variants (SNVs) in the EGFR gene, revealing resistance profiles against common tyrosine kinase inhibitors, thus enhancing our understanding of drug resistance in cancer (ref: Kim doi.org/10.1038/s41587-024-02465-z/). The combination of base and prime editing techniques has also been explored to assess the pathogenicity of variants in the EGFR gene, showcasing the versatility of CRISPR technologies in functional genomics (ref: Belli doi.org/10.1038/s41587-024-02439-1/). Additionally, advancements in CRISPR-based synthetic lethality screens have identified profound interactions between SNF2-family ATPases and DNA replication stress, emphasizing the potential of CRISPR in understanding genome maintenance (ref: Feng doi.org/10.1016/j.molcel.2024.10.016/).

The application of gene editing technologies in cancer therapy is rapidly evolving, with several studies showcasing innovative strategies. One notable advancement is the directed evolution of engineered virus-like particles (eVLPs), which enhance the delivery of gene editing agents. This system utilizes barcoded guide RNAs to label eVLP variants, facilitating the identification of those with improved transduction efficiencies (ref: Raguram doi.org/10.1038/s41587-024-02467-x/). In another study, the degradation of MYD88 in lymphomas harboring the MYD88 L265P mutation was achieved using Lasalocid A, highlighting a potential therapeutic strategy for targeting specific mutations in cancer (ref: Li doi.org/10.1182/blood.2024026781/). Additionally, the efficacy of CDK7 inhibitors in combination with other agents against myeloproliferative neoplasms transformed to acute myeloid leukemia (AML) was demonstrated, revealing synergistic effects that could enhance treatment outcomes (ref: Fiskus doi.org/10.1182/blood.2024026388/). Furthermore, CRISPR screening has elucidated the role of TRIM21 in promoting cell proliferation and drug resistance in pituitary adenomas, underscoring the potential of gene editing in unraveling cancer biology (ref: Liu doi.org/10.1093/neuonc/).

Research into the tumor microenvironment (TME) and its impact on immunotherapy resistance has revealed critical insights. A study identified that ovarian cancer-derived IL-4 contributes to immunotherapy resistance by creating an immunosuppressive TME dominated by macrophages, emphasizing the need for targeted therapies that can modulate this environment (ref: Mollaoglu doi.org/10.1016/j.cell.2024.10.006/). Another investigation explored how cancer cells restrict the immunogenicity of retrotransposon expression, with findings indicating that specific Alu repeat expressions can predict immune signaling pathways in pancreatic ductal adenocarcinoma (PDAC) patients (ref: Sun doi.org/10.1016/j.immuni.2024.10.015/). Additionally, the upregulation of Siglec15 in bladder cancer was shown to facilitate immune evasion, highlighting its potential as a therapeutic target to enhance the effectiveness of immunotherapies (ref: Deng doi.org/10.1186/s13045-024-01638-2/). The ablation of FAS in allogeneic CAR T cells was found to improve their survival in immunocompetent mice, suggesting a novel approach to enhance CAR T cell therapy (ref: Menegatti doi.org/10.1038/s41551-024-01282-8/).

The safety of genome editing technologies, particularly concerning off-target effects, remains a critical area of research. A study highlighted that the DNA-PKcs inhibitor AZD7648, while enhancing CRISPR-Cas9-directed homology-directed repair, also caused large-scale genomic alterations, including kilobase-scale deletions and translocations, raising concerns about its clinical application (ref: Cullot doi.org/10.1038/s41587-024-02488-6/). In contrast, research comparing the frequency of large DNA deletions during DNA repair revealed that base editors and prime editors induce such deletions at significantly lower rates than Cas9 nucleases, suggesting a potential advantage in terms of safety (ref: Hwang doi.org/10.1038/s41551-024-01277-5/). The development of CRISPRoffT, a comprehensive database of CRISPR/Cas off-targets, aims to enhance the accuracy of prediction algorithms and improve the safety of gene-editing therapies (ref: Wang doi.org/10.1093/nar/). Furthermore, the use of enhanced single-stranded DNA templates has shown to improve knock-in efficiencies in primary cells, indicating advancements in minimizing off-target effects (ref: Kanke doi.org/10.1093/nar/).

Recent advancements in gene editing techniques have significantly enhanced the precision and efficiency of genetic modifications. The development of high-throughput recruitment methods for transcriptional effectors has allowed for the systematic evaluation of protein domains that regulate gene expression across various genomic contexts (ref: Tycko doi.org/10.1038/s41587-024-02442-6/). Additionally, a new high-efficiency prime editing platform has been established, enabling multiplexed dropout screening and functional characterization of genetic variants, which is crucial for understanding gene function and disease mechanisms (ref: Cirincione doi.org/10.1038/s41592-024-02502-4/). The application of CRISPR-based synthetic lethality screens has also provided insights into the interactions between SNF2-family ATPases and DNA replication stress, further elucidating the complexities of genome maintenance (ref: Feng doi.org/10.1016/j.molcel.2024.10.016/). Moreover, the integration of CRISPR technologies with deep mutational scanning has facilitated the exploration of the fitness landscape of anti-CRISPR proteins, enhancing our understanding of microbial and phage co-evolution (ref: Stadelmann doi.org/10.1093/nar/).

Functional genomics utilizing CRISPR screens has emerged as a powerful tool for understanding gene function and interactions. Recent studies have employed saturation profiling to evaluate drug-resistant genetic variants in the EGFR gene, identifying resistance profiles that could inform therapeutic strategies against common tyrosine kinase inhibitors (ref: Kim doi.org/10.1038/s41587-024-02465-z/). The combination of base and prime editing techniques has enabled the assessment of a broad spectrum of variants in the EGFR gene, enhancing our ability to connect genetic variants to phenotypic outcomes (ref: Belli doi.org/10.1038/s41587-024-02439-1/). Additionally, the development of CRISPRoffT, a comprehensive database of off-target effects, aims to improve the accuracy of gene editing by providing essential data for researchers (ref: Wang doi.org/10.1093/nar/). Furthermore, the exploration of synthetic lethality between SMARCAL1 and FANCM through CRISPR screens has shed light on the mechanisms of DNA replication stress and genome integrity (ref: Feng doi.org/10.1016/j.molcel.2024.10.016/).

The ethical and regulatory landscape surrounding gene editing is evolving alongside advancements in technology. The iDog database has been established as a multi-omics resource for canids, integrating extensive genomic data to support canine research, which raises questions about data usage and genetic privacy (ref: Liu doi.org/10.1093/nar/). Similarly, the Solanaceae Information Resource (SoIR) addresses gaps in genomic data for economically important crops, highlighting the need for ethical considerations in agricultural biotechnology (ref: Liu doi.org/10.1093/nar/). The development of CRISPRoffT, a comprehensive database of off-target effects, emphasizes the importance of transparency and accuracy in gene editing applications, particularly in clinical settings (ref: Wang doi.org/10.1093/nar/). These resources not only facilitate research but also necessitate ongoing discussions about the implications of gene editing technologies on society and the environment.

Emerging applications of gene editing extend beyond traditional biomedical research, showcasing its potential in various fields. The iDog database serves as a comprehensive resource for studying domestic dogs and wild canids, integrating multi-omics data to support genetic research and breed improvement (ref: Liu doi.org/10.1093/nar/). Additionally, the Solanaceae Information Resource (SoIR) has been developed to provide a comprehensive genomics database for economically significant crops, facilitating comparative and functional genomic studies that can enhance agricultural productivity (ref: Liu doi.org/10.1093/nar/). The CRISPRoffT database further contributes to the understanding of off-target effects in gene editing, which is crucial for ensuring the safety and efficacy of gene editing applications in diverse fields (ref: Wang doi.org/10.1093/nar/). These advancements highlight the versatility of gene editing technologies and their potential to impact agriculture, veterinary science, and beyond.