The advancements in CRISPR and genome editing technologies have been significant, particularly with the introduction of novel methodologies and tools that enhance precision and efficiency. Zhou et al. explored the role of composite transposons with bivalent histone marks in regulating cell fate, utilizing CRISPR-Cas9 screening to identify genes that modify these marks, thereby influencing transcription (ref: Zhou doi.org/10.1016/j.cell.2025.07.014/). Park et al. addressed the limitations of prime editing efficiency by employing an AI-generated small binder to inhibit mismatch repair, which significantly improved editing outcomes (ref: Park doi.org/10.1016/j.cell.2025.07.010/). Furthermore, Wu et al. demonstrated that glycan shielding could enhance the persistence of CAR-T therapies in allogeneic settings, showcasing the potential of CRISPR in therapeutic applications (ref: Wu doi.org/10.1016/j.cell.2025.07.046/). The integration of deep learning in protein engineering, as reported by Yang et al., simplified the design of genome editing systems, leading to improved functionality and validation (ref: Yang doi.org/10.1016/j.cell.2025.07.037/). Sun et al. introduced programmable chromosome engineering (PCE) and RePCE, enabling scarless kilobase-to-megabase DNA manipulations, which represent a leap forward in genome editing capabilities (ref: Sun doi.org/10.1016/j.cell.2025.07.011/). Naert et al. utilized deep learning to predict repair processes at the genome-cargo interface, enhancing CRISPR-based DNA integration strategies (ref: Naert doi.org/10.1038/s41587-025-02771-0/). Biederstädt et al. conducted genome-wide CRISPR screens to identify targets that enhance CAR-NK cell antitumor potency, revealing critical checkpoints in immunosuppression (ref: Biederstädt doi.org/10.1016/j.ccell.2025.07.021/). Xu et al. developed targeted lipid nanoparticles for mRNA delivery to hematopoietic stem cells, facilitating in vivo genome editing for blood disorders (ref: Xu doi.org/10.1038/s41551-025-01480-y/). Lastly, Yu et al. presented GenomePAM, a method for scalable PAM characterization in mammalian cells, which is crucial for the development of Cas proteins (ref: Yu doi.org/10.1038/s41551-025-01464-y/). Wang et al. engineered a CRISPR-Cas12i tool for efficient multiplexed genome editing, addressing limitations in pre-crRNA processing (ref: Wang doi.org/10.1093/nar/).

Gene therapy continues to evolve, particularly in the context of treating complex diseases such as cancer and genetic disorders. Wang et al. reported on a phase 1 trial of allogeneic CD19-targeting T cells for systemic lupus erythematosus, demonstrating the potential of engineered T cell therapies to overcome the limitations of autologous approaches (ref: Wang doi.org/10.1038/s41591-025-03899-x/). Boutet et al. investigated the role of MLL3 mutations in breast cancer progression, revealing that loss of MLL3 promotes tumorigenesis through HIF1α-dependent mechanisms, highlighting the importance of genetic factors in cancer development (ref: Boutet doi.org/10.1016/j.immuni.2025.07.008/). Lu et al. characterized cis-regulatory elements in colorectal cancer using epigenomics and CRISPRi screenings, identifying functional variants that influence cell proliferation (ref: Lu doi.org/10.1038/s43018-025-01031-z/). Xu et al. further contributed to the field by developing a method for in vivo genome editing of hematopoietic stem cells using mRNA delivery, which showed promise for treating blood disorders (ref: Xu doi.org/10.1038/s41551-025-01480-y/). Chalumeau et al. introduced a prime editing strategy to reactivate fetal hemoglobin for sickle cell disease, achieving approximately 50% precise edits in hematopoietic cell lines (ref: Chalumeau doi.org/10.1182/blood.2024028166/). Radtke et al. evaluated the long-term efficiency of autologous base editing in rhesus macaques, paving the way for potential human applications (ref: Radtke doi.org/10.1126/scitranslmed.adn2601/). Zhou et al. identified an AHR-ELMSAN1 axis that optimizes BET-targeting therapy in leukemia, showcasing the potential for targeted therapies in cancer treatment (ref: Zhou doi.org/10.1126/scitranslmed.adn5400/). Cheng et al. identified AURKB as a therapeutic vulnerability in advanced gastrointestinal stromal tumors, emphasizing the need for novel treatment strategies (ref: Cheng doi.org/10.1084/jem.20250256/).

Cancer immunotherapy is rapidly advancing, with new strategies being developed to enhance the efficacy of existing treatments. Biederstädt et al. conducted genome-wide CRISPR screens to identify critical targets that can enhance the antitumor potency of CAR-NK cells, revealing important checkpoints that regulate resistance to immunosuppressive environments (ref: Biederstädt doi.org/10.1016/j.ccell.2025.07.021/). Feng et al. introduced MCB-294, a dual-state pan-KRAS inhibitor that binds both active and inactive forms of KRAS, demonstrating multifaceted anti-tumor efficacy in KRAS-driven cancers (ref: Feng doi.org/10.1016/j.ccell.2025.07.006/). Salgia et al. performed comprehensive tumor-immune profiling of sarcomatoid renal cell carcinoma, uncovering mediators of paradoxical immune sensitivity that could inform treatment strategies (ref: Salgia doi.org/10.1016/j.ccell.2025.07.010/). Sun et al. presented iterative recombinase technologies that facilitate efficient and precise genome engineering across kilobase to megabase scales, addressing challenges in large-scale DNA manipulations (ref: Sun doi.org/10.1016/j.cell.2025.07.011/). The integration of organic afterglow emitters for visual observation of hydrogel formation in biomedical systems was reported by Mo et al., which could enhance the efficacy of hydrogel applications in cancer therapy (ref: Mo doi.org/10.1002/adma.202418750/). Liu et al. developed a dual-mode Janus bioaerogel for atmospheric water harvesting, which could have implications for cancer treatment environments by ensuring hydration (ref: Liu doi.org/10.1002/adma.202512244/). Wang et al. designed a nature-inspired MXene electrode that enhances ion transport in electrochemical systems, potentially benefiting cancer treatment delivery systems (ref: Wang doi.org/10.1002/adma.202511444/).

Transcriptional regulation and enhancer studies have gained prominence in understanding gene expression dynamics. Cheng et al. introduced MAPIT-seq, a method for co-profiling RNA-protein interactions and transcriptomes in single cells, which allows for a deeper understanding of RNA-binding protein regulation (ref: Cheng doi.org/10.1038/s41592-025-02774-4/). The JUMP Cell Painting Consortium, as reported by Chandrasekaran et al., generated a comprehensive morphological map by perturbing a significant portion of the human protein-coding genome, providing insights into gene function and cellular states (ref: Chandrasekaran doi.org/10.1038/s41592-025-02753-9/). Southard et al. demonstrated that systematic activation of transcription factors can recreate distinct transcriptional states in fibroblasts, offering a model for studying gene regulation (ref: Southard doi.org/10.1038/s41588-025-02284-1/). Bi et al. conducted high-throughput CRISPR interference screening to decode functional enhancer connectomes in glioma, revealing the role of enhancer-associated genetic variations in tumor progression (ref: Bi doi.org/10.1038/s41556-025-01737-3/). Margolis et al. explored the crosstalk between different CRISPR-Cas types, showing how type VI-A adaptation is primed by type I systems, which highlights the complexity of CRISPR-mediated immunity (ref: Margolis doi.org/10.1016/j.chom.2025.05.020/). Smith et al. found that type I interference generates substrates for type III adaptation, indicating a cooperative mechanism between these systems (ref: Smith doi.org/10.1016/j.chom.2025.07.021/).

CRISPR screening and functional genomics have emerged as powerful tools for elucidating gene function and regulatory mechanisms. Cattle et al. enhanced the Eco1 retron editor, enabling precision genome engineering in human cells without double-strand breaks, which addresses previous limitations in efficiency (ref: Cattle doi.org/10.1093/nar/). Liu et al. developed TaqTth-hpRNA, a novel DNA editing tool that efficiently cleaves genomic DNA without stringent sequence motifs, demonstrating high efficiency in Escherichia coli (ref: Liu doi.org/10.1093/nar/). Xue et al. provided insights into the structural basis of nucleosome binding by RFX5, revealing its role in nucleosome remodeling, which is crucial for understanding transcriptional regulation (ref: Xue doi.org/10.1093/nar/). Migliori et al. introduced ONE-STEP tagging, a method for rapid site-specific integration, achieving high integration efficiency in various cell types (ref: Migliori doi.org/10.1093/nar/). Desai et al. explored echocardiographic changes in patients with nonobstructive hypertrophic cardiomyopathy, contributing to the understanding of cardiac biomarkers in disease contexts (ref: Desai doi.org/10.1016/j.jacc.2025.08.019/). The insights gained from these studies underscore the potential of CRISPR technologies in advancing functional genomics and therapeutic applications.

Synthetic biology and engineering approaches are revolutionizing the development of innovative solutions for various biomedical applications. Liu et al. presented a diamond-inspired DNA hydrogel designed for burn wound healing, addressing the challenges of prolonged healing processes associated with burn injuries (ref: Liu doi.org/10.1002/adma.202509727/). Zhong et al. developed double heterostructures for monolayer materials, achieving record quantum efficiency, which could enhance optoelectronic devices (ref: Zhong doi.org/10.1002/adma.202506125/). Wu et al. engineered a pseudo-charge transfer absorption mechanism in organic photodetectors, optimizing device performance for narrowband short-wave infrared detection (ref: Wu doi.org/10.1002/adma.202509521/). Smith et al. explored the interactions between type I and type III CRISPR-Cas systems, revealing how type I immunity can prime type III spacer acquisition, which has implications for understanding CRISPR-mediated defense mechanisms (ref: Smith doi.org/10.1016/j.chom.2025.07.021/). Mohseni et al. introduced ALLEGRO, a machine learning algorithm for designing CRISPR guide RNA libraries across diverse taxa, which could significantly advance genetic research (ref: Mohseni doi.org/10.1093/nar/). Nourisson et al. investigated the fidelity and specialization of DNA polymerases involved in programmed double-strand break repair in Paramecium, contributing to our understanding of DNA repair mechanisms (ref: Nourisson doi.org/10.1093/nar/).

Base editing and precision genome engineering have made remarkable strides, enabling targeted modifications with high accuracy. Li et al. engineered high-precision C-to-G base editors, demonstrating enhanced editing efficiency through truncations of the CDA1 C-terminus, applicable across various cell types including human and rice cells (ref: Li doi.org/10.1093/nar/). Zhou et al. developed a rapid red-light-activated Cre recombinase system, REDMAPCre, which allows for precise genome engineering in mammalian cells with significantly improved activation kinetics (ref: Zhou doi.org/10.1093/nar/). Desai et al. provided insights from the ODYSSEY-HCM trial, evaluating the effects of mavacamten on cardiac biomarkers in nonobstructive hypertrophic cardiomyopathy, which may inform future therapeutic strategies (ref: Desai doi.org/10.1016/j.jacc.2025.08.017/). These studies collectively highlight the advancements in base editing technologies and their potential applications in treating genetic disorders and improving therapeutic outcomes.

The integration of machine learning and AI in genomics is transforming the landscape of genetic research and precision medicine. Xu et al. developed AlphaCD, a machine learning model that accurately characterizes cytidine deaminases, providing insights into catalytic efficiency and off-target activity, which is crucial for the design of genome editing tools (ref: Xu doi.org/10.1038/s41422-025-01164-x/). Wang et al. engineered a CRISPR-Cas12i tool for efficient multiplexed genome editing, addressing challenges in pre-crRNA processing and enhancing the capabilities of CRISPR technologies (ref: Wang doi.org/10.1093/nar/). Cattle et al. enhanced the Eco1 retron editor, enabling precision genome engineering in human cells without double-strand breaks, which is a significant advancement in the field (ref: Cattle doi.org/10.1093/nar/). Jaworski et al. investigated the replication dynamics of extrachromosomal DNA, providing insights into its role in cancer progression and therapeutic resistance (ref: Jaworski doi.org/10.1093/nar/). Pavlova et al. explored the role of G-quadruplexes in superenhancer dynamics, revealing their potential as targets for therapeutic intervention (ref: Pavlova doi.org/10.1093/nar/). These studies underscore the potential of machine learning and AI to enhance our understanding of genomic functions and improve the precision of genetic engineering.