The advent of CRISPR and genome editing technologies has revolutionized molecular biology, enabling precise modifications in genetic sequences. A notable advancement is the integration of CRISPR with spatial transcriptomics, as demonstrated by Binan et al., who utilized Perturb-FISH to uncover transcriptional circuits in monocytes responding to lipopolysaccharide. This method revealed both intracellular and intercellular regulatory mechanisms, highlighting the potential of combining imaging techniques with CRISPR screening (ref: Binan doi.org/10.1016/j.cell.2025.02.012/). Furthermore, Fan et al. explored the use of transcription activator-like effector-linked deaminases (TALEDs) for adenine base editing in mitochondrial DNA, elucidating the role of base excision repair in facilitating this process (ref: Fan doi.org/10.1038/s41587-025-02608-w/). In a different approach, Tang et al. developed Cas12a-knock-in mice, which allow for multiplexed genome editing and disease modeling without causing discernible pathology, thus providing a robust platform for studying gene interactions (ref: Tang doi.org/10.1038/s41551-025-01371-2/). Zeng et al. introduced a computational framework to identify immunotherapy targets, emphasizing the dual functionality of certain genes in both cancer and immune cells, with TNFAIP3 emerging as a promising target (ref: Bi doi.org/10.1016/j.immuni.2025.02.016/). Additionally, Wang et al. combined CRISPR-Cas9 screening with single-cell RNA sequencing to investigate the transdifferentiation of prostate cancer, revealing the epigenetic role of ZMYND8 in this process (ref: Wang doi.org/10.1038/s43018-025-00928-z/). The versatility of CRISPR technologies is further highlighted by Schmidt et al., who optimized dCas9 ribonucleoprotein complexes for efficient transcriptomic manipulation without DNA or viral vectors (ref: Schmidt doi.org/10.1093/nar/). Lastly, Whitford et al. demonstrated the efficacy of CASCADE-Cas3 systems for genome engineering in Streptomyces, showcasing the advantages of type I CRISPR systems over traditional type II systems (ref: Whitford doi.org/10.1093/nar/).

Gene therapy has emerged as a promising approach to treat genetic disorders and enhance therapeutic efficacy in cancer. Luo et al. developed a computational platform that integrates CRISPR screen datasets and RNA sequencing to identify therapeutic targets that can simultaneously affect cancer cells and T cells, thus enhancing anti-tumor immunity (ref: Luo doi.org/10.1016/j.immuni.2025.02.007/). This dual-action approach is crucial as many cancer therapies inadvertently impair immune function. In the realm of wound healing, Wang et al. introduced an electroactive dressing that selectively manages exudate while promoting cell activity, addressing the challenges of traditional dressings that can hinder healing (ref: Wang doi.org/10.1002/adma.202413320/). Huo et al. further explored drug-delivery systems, proposing a novel conduit that enhances nerve regeneration by overcoming barriers that limit drug efficacy (ref: Huo doi.org/10.1002/adma.202413992/). In the context of mRNA therapeutics, Xiao et al. reported on high-density brush-shaped polymer lipids that reduce anti-PEG antibody binding, thus improving the consistency of protein production during repeated dosing (ref: Xiao doi.org/10.1038/s41563-024-02116-3/). Additionally, Qiao et al. developed engineered bacteria capable of controlled expression of cancer therapeutics using near-infrared light, showcasing innovative strategies for targeted cancer treatment (ref: Qiao doi.org/10.1038/s43018-025-00932-3/). The advancements in gene therapy are further complemented by Tang et al.'s work on Cas12a-knock-in mice, which facilitate multiplexed gene editing and modeling of genetic disorders (ref: Tang doi.org/10.1038/s41551-025-01371-2/).

Cancer research continues to evolve with innovative approaches to understand and combat the disease. Choi et al. conducted extensive sequencing in over 50,000 cases to identify genetic variations associated with atrial fibrillation, revealing novel links between these variations and cardiomyopathies, thus expanding the understanding of cancer's genetic architecture (ref: Choi doi.org/10.1038/s41588-025-02074-9/). Luo et al. emphasized the importance of global collaborations in translational cancer research, advocating for shared resources and harmonized regulatory frameworks to enhance the translation of laboratory findings into clinical applications (ref: Luo doi.org/10.1016/j.ccell.2025.02.005/). Zeng et al. utilized CRISPR screens to identify immunotherapy targets, highlighting TNFAIP3 as a dual-function gene that enhances anti-tumor responses when ablated (ref: Bi doi.org/10.1016/j.immuni.2025.02.016/). Liu et al. focused on the role of somatic mutations in modulating cancer immunotherapy responses, particularly in the context of PD-1/PD-L1 blockade, underscoring the need for systematic interpretations of immune-related mutations (ref: Liu doi.org/10.1038/s41392-025-02171-5/). Additionally, Tang et al.'s Cas12a-knock-in mice provide a valuable tool for studying complex gene interactions in cancer, while Mao et al. raised concerns about the accuracy of CRISPR-based imaging tools due to spurious RNA transcripts, which can lead to false-positive results in genomic imaging (ref: Mao doi.org/10.1093/nar/). Yang et al. investigated the impact of CREBBP mutations in lymphomas, revealing how these mutations affect enhancer activation and chromatin interactions, which could inform therapeutic strategies (ref: Yang doi.org/10.1182/blood.2024026664/).

Mitochondrial and metabolic research is crucial for understanding various diseases, including neurodegenerative disorders. Fan et al. explored the mechanisms of adenine base editing in mitochondrial DNA using TALEDs, revealing that base excision repair is essential for efficient editing (ref: Fan doi.org/10.1038/s41587-025-02608-w/). Cheng et al. highlighted the connection between mitochondrial respiratory complex IV deficiency and amyotrophic lateral sclerosis (ALS), noting that approximately half of sporadic ALS cases exhibit defects in this complex, suggesting a potential therapeutic target (ref: Cheng doi.org/10.1038/s41593-025-01896-4/). Ray et al. investigated the effects of solbinsiran, an RNA-based therapy targeting ANGPTL3, demonstrating its impact on lipid levels in preclinical models and early human studies, which could have implications for metabolic disorders (ref: Ray doi.org/10.1016/j.jacc.2025.03.005/). Xiao et al. also contributed to the field by developing high-density brush-shaped polymer lipids that mitigate anti-PEG antibody responses, enhancing the efficacy of mRNA therapeutics (ref: Xiao doi.org/10.1038/s41563-024-02116-3/). Wang et al. introduced an electroactive dressing for wound healing, which selectively manages exudate and promotes cell activity, addressing the challenges faced in tissue regeneration (ref: Wang doi.org/10.1002/adma.202413320/). Together, these studies underscore the importance of mitochondrial function and metabolic pathways in both therapeutic development and disease understanding.

RNA biology and editing have gained significant attention due to their roles in gene regulation and disease. Li et al. developed RIAN-seq, a novel technique for mapping R-loops at base-pair resolution, which revealed a higher prevalence of R-loops than previously detected, thus providing insights into their biological functions (ref: Li doi.org/10.1016/j.molcel.2025.02.019/). Zhao et al. investigated the role of o8G-modified circPLCE1 in lung cancer, demonstrating that this modification inhibits cancer progression through chaperone-mediated autophagy, highlighting the importance of RNA modifications in cancer biology (ref: Zhao doi.org/10.1186/s12943-025-02283-0/). Vasquez et al. focused on the functional characterization of MUTYH variants associated with colorectal cancer, utilizing precision genome editing to enhance the understanding of these genetic variants (ref: Vasquez doi.org/10.1093/nar/). Miceli et al. introduced MAIGRET, a CRISPR-based immunoassay for detecting antibodies and antigens, showcasing the potential of RNA-based technologies in diagnostics (ref: Miceli doi.org/10.1093/nar/). Furthermore, Li et al. developed a self-contained G-quadruplex/hemin DNAzyme for in situ imaging analysis, demonstrating the versatility of RNA and DNA structures in bioanalysis (ref: Li doi.org/10.1093/nar/). These studies collectively emphasize the critical roles of RNA in cellular processes and their potential applications in therapeutic and diagnostic contexts.

Translational research is essential for bridging the gap between laboratory discoveries and clinical applications. Luo et al. highlighted the significance of global alliances in cancer research, advocating for collaborative efforts to enhance the translation of findings into effective therapies (ref: Luo doi.org/10.1016/j.ccell.2025.02.005/). Choi et al. identified novel genetic variations associated with atrial fibrillation through extensive sequencing, which could inform future therapeutic strategies and patient management (ref: Choi doi.org/10.1038/s41588-025-02074-9/). Fan et al. explored the mechanisms of adenine base editing in mitochondrial DNA, providing insights that could lead to innovative therapies for genetic disorders (ref: Fan doi.org/10.1038/s41587-025-02608-w/). Pang et al. investigated the role of CHEK1 in colorectal cancer, revealing its upregulation in malignant cells and potential as a therapeutic target (ref: Pang doi.org/10.5306/wjco.v16.i3.101725/). Li et al. developed RIAN-seq, a technique for mapping R-loops, which could have implications for understanding gene regulation and disease mechanisms (ref: Li doi.org/10.1016/j.molcel.2025.02.019/). These studies collectively underscore the importance of integrating basic research with clinical applications to improve patient outcomes and advance therapeutic strategies.

Epigenetics and gene regulation play pivotal roles in cellular function and development. Liesenfelder et al. investigated the effects of epigenetic editing at age-associated CpGs, revealing that targeted modifications can induce genome-wide bystander effects, thereby influencing the aging process (ref: Liesenfelder doi.org/10.1038/s43587-025-00841-1/). Wu et al. explored the incorporation of spiro units in thermally activated delayed fluorescence (TADF) emitters, demonstrating that such modifications can enhance the efficiency of organic light-emitting diodes (ref: Wu doi.org/10.1002/anie.202504723/). Rao et al. examined the role of Argonaute CSR-1A in maintaining H3K9me3 levels, which is crucial for protecting somatic development in offspring, thus linking parental stress to epigenetic inheritance (ref: Rao doi.org/10.1093/nar/). Lin et al. focused on optimizing gRNA selection for CRISPR screening, enabling high-penetrance phenotypic outcomes in model organisms, which is essential for interrogating gene functions related to diseases (ref: Lin doi.org/10.1093/nar/). These studies highlight the intricate connections between epigenetic modifications and gene regulation, emphasizing their significance in development, disease, and therapeutic interventions.

The development of novel delivery systems for therapeutics is crucial for enhancing treatment efficacy and patient outcomes. Wang et al. introduced an electroactive dressing that selectively manages exudate in wound healing, promoting cell activity and addressing the limitations of traditional dressings (ref: Wang doi.org/10.1002/adma.202413320/). Huo et al. proposed a drug-delivery nerve conduit that overcomes barriers to nerve regeneration, highlighting the importance of multifunctional systems in therapeutic applications (ref: Huo doi.org/10.1002/adma.202413992/). Luo et al. developed a computational platform for identifying therapeutic targets that act on both cancer and immune cells, integrating CRISPR screen data and RNA sequencing to enhance therapeutic strategies (ref: Luo doi.org/10.1016/j.immuni.2025.02.007/). Pang et al. investigated the expression of CHEK1 in colorectal cancer, providing insights into its potential as a therapeutic target (ref: Pang doi.org/10.5306/wjco.v16.i3.101725/). Song et al. presented a dual-stimuli-responsive DNA nanoframework for spatially controlled co-delivery of diagnostic and therapeutic agents, showcasing innovative strategies for precision therapy in pancreatic cancer (ref: Song doi.org/10.1002/anie.202500566/). These advancements in delivery systems underscore the importance of integrating novel technologies to improve therapeutic efficacy and patient care.