The exploration of CRISPR and RNA editing technologies has advanced significantly, particularly with the development of RNA-targeting systems like Cas13. Zilberzwige-Tal et al. provide insights into the evolutionary origins of Cas13, suggesting it evolved from the AbiF toxin-antitoxin system, which is linked to a conserved non-coding RNA (ref: Zilberzwige-Tal doi.org/10.1016/j.cell.2025.01.034/). This evolutionary perspective is complemented by studies demonstrating the practical applications of CRISPR systems in live-cell imaging. For instance, Xia et al. introduced a novel approach called single-molecule live-cell fluorescence in situ hybridization (smLiveFISH), which utilizes the CRISPR-Csm complex for real-time visualization of RNA molecules, showcasing its effectiveness across various cell types (ref: Xia doi.org/10.1038/s41587-024-02540-5/). Additionally, the work by Sun et al. on SCISSOR technology highlights the potential for flexible RNA excision through engineered guide RNAs, marking a shift from traditional single-base editing techniques (ref: Sun doi.org/10.1016/j.molcel.2025.01.021/). These advancements not only enhance our understanding of RNA dynamics but also pave the way for innovative therapeutic strategies. Furthermore, the role of anti-CRISPR proteins, such as AcrVIB1, in modulating CRISPR-Cas13b immunity is crucial, as demonstrated by Wandera et al., who elucidated how AcrVIB1 promotes unproductive crRNA binding, thereby influencing CRISPR efficacy (ref: Wandera doi.org/10.1016/j.molcel.2025.01.020/). Overall, the integration of evolutionary insights, imaging techniques, and regulatory mechanisms underscores the multifaceted nature of CRISPR technologies in RNA editing.

Gene editing technologies, particularly CRISPR, are increasingly being harnessed for cancer therapy, with promising results in enhancing T cell therapies and targeting specific oncogenic pathways. Chang et al. introduced SEED-Selection, a novel method that enriches primary T cells edited at multiple loci, thereby improving the efficacy of cellular therapies (ref: Chang doi.org/10.1038/s41587-024-02531-6/). This method allows for the selective removal of non-modified cells while preserving those with desired genetic modifications, which is critical for developing effective immunotherapies. In a different approach, Wang et al. explored the potential of targeting ADAR1 as a therapeutic strategy for prostate cancer, revealing that inhibiting this RNA editing enzyme could be a viable treatment option (ref: Wang doi.org/10.1038/s43018-025-00907-4/). The study highlights the need for targeted therapies that can effectively manage cancer progression. Additionally, Shapiro et al. reported on a phase I trial combining memory-like NK cells with an IL-15 super-agonist and CTLA-4 blockade in advanced head and neck cancer, demonstrating safety and enhanced NK cell proliferation (ref: Shapiro doi.org/10.1186/s13045-025-01669-3/). These findings collectively emphasize the potential of gene editing to not only enhance existing therapies but also to introduce novel strategies for combating cancer, particularly through the manipulation of immune cell functions.

Epigenetic editing has emerged as a powerful tool for regulating gene expression without altering the underlying DNA sequence, with significant implications for therapeutic applications. Tremblay et al. developed an epigenetic editor targeting PCSK9, achieving durable reductions in LDL cholesterol levels through induced DNA methylation (ref: Tremblay doi.org/10.1038/s41591-025-03508-x/). This study underscores the potential of epigenetic modifications in managing metabolic disorders. Moreover, Rohm et al. investigated the activation of the imprinted Prader-Willi syndrome locus using CRISPR-based epigenome editing, revealing critical insights into gene regulation mechanisms that could inform therapeutic strategies for genetic disorders (ref: Rohm doi.org/10.1016/j.xgen.2025.100770/). In a broader context, the work by Zheng et al. on the compact CRISPR-Cas effector Cas12h1 highlights its unique PAM recognition and nickase activity, which could be leveraged for precise epigenetic editing (ref: Zheng doi.org/10.1038/s41392-025-02147-5/). Collectively, these studies illustrate the versatility of epigenetic editing technologies in modulating gene expression and their potential for treating a variety of diseases, including genetic disorders and metabolic conditions.

CRISPR technologies are revolutionizing basic research and functional genomics by enabling precise gene editing and functional analysis of genetic elements. Carreño-Tarragona et al. explored the influence of the JAK2 46/1 haplotype on PD-L1 expression, linking genetic variations to immune responses in myeloproliferative neoplasms (ref: Carreño-Tarragona doi.org/10.1182/blood.2023023787/). This highlights the importance of understanding genetic factors in disease susceptibility. Additionally, Yousefian-Jazi et al. investigated the loss of MEF2C function due to enhancer mutations, revealing its role in mitochondrial dysfunction and motor deficits in mice, which has implications for understanding neurodegenerative diseases (ref: Yousefian-Jazi doi.org/10.1186/s13024-024-00792-y/). Furthermore, Fu et al. examined the dynamic properties of transcriptional condensates in CRISPRa-mediated gene activation, providing insights into the mechanisms of transcriptional regulation (ref: Fu doi.org/10.1038/s41467-025-56735-8/). These studies collectively demonstrate the utility of CRISPR in elucidating complex genetic interactions and regulatory mechanisms, paving the way for advancements in functional genomics and therapeutic interventions.

The development of innovative delivery systems for gene editing is crucial for enhancing the efficacy and specificity of therapeutic applications. Hofstraat et al. introduced a nature-inspired platform nanotechnology for RNA delivery to myeloid cells, demonstrating its effectiveness in delivering siRNA and mRNA for gene editing (ref: Hofstraat doi.org/10.1038/s41565-024-01847-3/). This approach leverages natural lipoproteins to facilitate the delivery of nucleic acids, which is essential for achieving targeted gene modulation in vivo. In a complementary study, Nyberg et al. utilized an evolved adeno-associated virus variant, Ark313, for in vivo engineering of murine T cells, showcasing its potential for gene editing in immune cells (ref: Nyberg doi.org/10.1016/j.immuni.2025.01.009/). This method allows for the integration of large DNA donor templates, which is critical for effective gene therapy. Additionally, Zheng et al. characterized the compact CRISPR-Cas effector Cas12h1, which exhibits broad-spectrum PAM recognition, further enhancing the toolbox available for gene editing applications (ref: Zheng doi.org/10.1038/s41392-025-02147-5/). Together, these innovations in delivery systems are paving the way for more effective and targeted gene editing strategies, with significant implications for therapeutic development.

The intersection of CRISPR technology and immune responses is a rapidly evolving area of research, with implications for both understanding immune mechanisms and developing novel therapies. He et al. identified the role of phosphoseryl-transfer RNA kinase (PSTK) in acute myeloid leukemia (AML) through a CRISPR-CRISPR-associated protein 9 screen, revealing its potential as a therapeutic target (ref: He doi.org/10.1182/blood.2024026040/). This study underscores the importance of metabolic dependencies in leukemic stem cells and how CRISPR can be utilized to dissect these pathways. Additionally, Luo et al. conducted a population-based study assessing global trends in lung cancer incidence, highlighting the impact of environmental factors on cancer development (ref: Luo doi.org/10.1016/S2213-2600(24)00428-4/). This research emphasizes the need for integrating genetic and environmental data to understand cancer etiology better. Furthermore, the development of biomimetic membranes for precise ion separation, as reported by Lv et al., showcases innovative approaches to enhance therapeutic delivery systems (ref: Lv doi.org/10.1002/adma.202419496/). Collectively, these studies illustrate the multifaceted role of CRISPR in elucidating immune responses and developing targeted therapies.

Understanding the mechanisms underlying CRISPR-Cas systems is essential for harnessing their potential in gene editing and therapeutic applications. Yin et al. investigated the regulation of CRISPR trans-cleavage activity by overhanging activators, revealing how structural features influence the activation timing and efficiency of Cas12a (ref: Yin doi.org/10.1093/nar/). This study highlights the intricate regulatory mechanisms that can be exploited to enhance CRISPR functionality. Additionally, Li et al. explored the role of intrinsically disordered regions (IDRs) in gene regulation, demonstrating that synthetic dCas9-IDR fusions can stimulate endogenous gene expression through chromatin interactions (ref: Li doi.org/10.1093/nar/). This research provides insights into the potential of CRISPR technologies to manipulate gene expression at a fundamental level. Furthermore, Wandera et al. characterized the anti-CRISPR protein AcrVIB1, elucidating its mechanism of inhibiting CRISPR-Cas13b immunity by promoting unproductive crRNA binding (ref: Wandera doi.org/10.1016/j.molcel.2025.01.020/). These findings collectively enhance our understanding of CRISPR-Cas systems and their regulatory networks, paving the way for more effective gene editing strategies.

CRISPR technology is playing a transformative role in genetic engineering, particularly in stem cell research and therapy. Chang et al. developed SEED-Selection, a method that enables the enrichment of primary T cells edited at multiple loci, enhancing the potential for effective cellular therapies (ref: Chang doi.org/10.1038/s41587-024-02531-6/). This innovative approach addresses the challenge of heterogeneity in engineered cell populations, which is crucial for advancing immunotherapy. In another study, Fagerberg et al. utilized CRISPR-Cas9-based perturbation sequencing to investigate the role of transcription factors in CD8 T cell fate decisions during acute viral infections, revealing insights into lineage fidelity and exhaustion mechanisms (ref: Fagerberg doi.org/10.1126/science.adn2337/). This research underscores the importance of understanding stem cell differentiation pathways for developing targeted therapies. Additionally, Lin et al. demonstrated that multiplexed epigenetic memory editing using CRISPRoff could sensitize glioblastoma cells to chemotherapy, highlighting the potential of epigenetic strategies in cancer treatment (ref: Lin doi.org/10.1093/neuonc/). Collectively, these studies illustrate the significant advancements in genetic engineering facilitated by CRISPR technology, particularly in the context of stem cell research and therapeutic applications.