Frontiers in genome editing最新文献

{"title":"Rewriting the script: gene therapy and genome editing for von Willebrand Disease.","authors":"Alastair Barraclough, Isabel Bär, Tirsa van Duijl, Karin Fijnvandraat, Jeroen C J Eikenboom, Frank W G Leebeek, Ruben Bierings, Jan Voorberg, Despoina Trasanidou","doi":"10.3389/fgeed.2025.1620438","DOIUrl":"10.3389/fgeed.2025.1620438","url":null,"abstract":"<p><p>In recent years gene therapy has emerged as a powerful technology for treatment of a large variety of inherited disorders. With the FDA approval of <i>in vivo</i> gene therapy of hemophilia A and B using AAV-mediated transgene delivery to hepatocytes, the path towards a new treatment era seemed paved. Also, CRISPR-Cas based approaches have reached the clinic, as in the <i>ex vivo</i> treatment of hematopoietic stem cells for sickle cell disease and thalassemia patients. The question arises whether these innovative strategies will also be suitable for patients with von Willebrand Disease (VWD). Whilst <i>in</i> and <i>ex vivo</i> delivery to endothelial cells (ECs) has been demonstrated, and CRISPR-Cas9 gene editing has been successful in ECs, there are currently no gene therapy options available for VWD. The wide variety of pathogenic VWF mutations makes development of broadly applicable, cost-effective gene therapies challenging. While delivery of von Willebrand factor (VWF) as a therapeutic transgene would be optimal, the size of VWF challenges efficient delivery. Therefore, treatment of VWD requires targeted, personalized gene therapy; for instance by using the newest CRISPR-Cas technologies which can be tailored to facilitate alteration and restoration of various pathogenic VWD variants. This review describes the inherited bleeding disorder VWD and potential gene therapy approaches for management of the disease. Thereby we are exploring different CRISPR-Cas technologies and recent developments in the field. Moreover, we will discuss the ongoing advances of <i>in vivo</i> delivery systems, all with the scope on ECs.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1620438"},"PeriodicalIF":5.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12497766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-stranded DNA (ssDNA) donor repair templates and CRISPR/Cas9 enable a high-frequency of targeted insertions in potato.","authors":"Matías N González, Neha Salaria, Martin Friberg, Ying Liu, Josefin Alverup, Mariette Andersson, Per Hofvander","doi":"10.3389/fgeed.2025.1661829","DOIUrl":"10.3389/fgeed.2025.1661829","url":null,"abstract":"<p><p>Homology-directed repair (HDR) holds great promise for plant genetic engineering but remains challenging due to its inherently low efficiency in gene editing applications. While studies in animal systems suggest that the structure of the donor repair template (DRT) influences HDR efficiency, this parameter remains largely unexplored in plants. In this study, we combined protoplast transfection with next-generation sequencing to analyse the impact of DRT structure on HDR efficiency in potato. A highly efficient ribonucleoprotein (RNP) complex targeting the <i>soluble starch synthase 1</i> (<i>SS1</i>) gene was used in combination with various DRTs, differing in structural factors such as homology arm (HA) length, strandedness (i.e., ssDNA vs. dsDNA), and sequence orientation in ssDNA donors. Our results indicate that a ssDNA donor in the target orientation outperformed other configurations, achieving a HDR efficiency of 1.12% of the sequencing reads in the pool of protoplasts. Interestingly, HDR efficiency appeared independent of HA length. Notably, a ssDNA donor with HAs as short as 30 nucleotides led to targeted insertions in up to 24.89% of reads on average, but predominantly via alternative imprecise repair pathways, such as microhomology-mediated end joining (MMEJ). This donor structure also consistently yielded the highest HDR and targeted insertion rates at two out of three additional loci tested, offering valuable insights for future genome editing strategies in potato. We further assessed strategies to favour HDR over alternative repair outcomes, including the use of small molecules known to inhibit competing pathways in animal systems, and modifications to DRTs to enhance their availability in the vicinity of the target site. However, these approaches did not improve HDR efficiency. Overall, this study presents an effective platform for rapidly assessing gene editing components in potato and provides insights for achieving high-frequency, targeted insertions of short DNA fragments, especially relevant for efficient knock-in integration in non-coding genomic regions.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1661829"},"PeriodicalIF":4.4,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR activation: identifying and using novel genes for plant disease resistance breeding.","authors":"John E McLaughlin, Idrice Carther Kue Foka, Michael A Lawton, Rong Di","doi":"10.3389/fgeed.2025.1596600","DOIUrl":"10.3389/fgeed.2025.1596600","url":null,"abstract":"<p><p>CRISPR-based technologies have revolutionized plant science by enabling precise modulation of gene function, including CRISPR activation (CRISPRa), a recently emerging strategy which shows particular promise for enhancing disease resistance through targeted gene upregulation. Unlike conventional CRISPR editing, which introduces double-stranded DNA breaks and permanent genomic changes, CRISPRa employs a deactivated Cas9 (dCas9) fused to transcriptional activators. This system allows quantitative and reversible gene activation without altering the DNA sequence, offering a gain-of-function (GOF) like enhanced blight resistance in staple crops. Despite its potential, the limited adoption of CRISPRa in plant biology to date underscores the need for future studies to fully harness its capabilities for crop improvement. This review addresses the groundbreaking and relatively underexplored potential of CRISPR activation (CRISPRa) systems for GOF studies in plant biology, and advocates for the adoption of CRISPRa to discover and harness genetic variation for enhancing disease resistance. We present recent advancements in CRISPRa technology, emphasizing its successful application in boosting plant immunity. Moreover, we discuss the synergistic potential of integrating CRISPRa with functional genomics tools such as genome-wide association studies (GWAS) and multi-omics approaches to identify and characterize key resistance genes. Additionally, we highlight ongoing progress in developing plant-specific programmable transcriptional activators (PTAs) to optimize CRISPRa efficiency. Challenges associated with achieving transgene-free overexpression and the deployment of alternative CRISPR systems are also explored. Together, these advances position CRISPRa as a transformative tool for future crop breeding strategies aimed at achieving durable, broad-spectrum disease resistance and sustainability in agriculture.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1596600"},"PeriodicalIF":5.9,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In pursuit of an HIV cure: from stem cell transplants to gene therapies.","authors":"Jennifer Clees, Maya Basic, Pedro E Cruz, Servio H Ramirez, Allison M Andrews","doi":"10.3389/fgeed.2025.1634193","DOIUrl":"10.3389/fgeed.2025.1634193","url":null,"abstract":"<p><p>Since 2009, seven people living with human immunodeficiency virus (PLHIV) have been declared cured of HIV after receiving allogeneic hematopoietic stem cell transplants (alloHSCTs) to treat hematologic malignancies. In this sense, cure signifies the absence of viral DNA/RNA and undetectable viral loads without the use of antiretroviral therapy (ART). Five of these transplants utilized mutated C-C motif chemokine receptor type 5 (CCR5^Δ32/Δ32) stem cells. Much has been learned from these and past cases, and although effective, bone marrow transplants cannot be easily or safely translated to cure the millions of PLHIV across the globe. A successful eradicating cure includes both the prevention of HIV from entering new cells and the elimination of tissue reservoirs. Protecting hematopoietic stem and progenitor cells (HSPCs) from infection is a key consideration since there is evidence that HSPCs themselves, not only their descendants, are susceptible to infection. Gene therapy approaches have the potential to bring about an eradicating HIV cure that could be highly effective, broadly applicable, less expensive, and practical to implement. Current strategies are tackling this problem by removing the integrated proviral DNA from infected cells and/or eliminating the co-receptor(s) necessary for HIV viral entry into target cells. Both approaches hold promise, but they require overcoming key challenges (i.e., vector toxicity, transduction efficacy, elimination of reservoir cells, etc.). This review summarizes and examines the lessons learned about curing HIV through bone marrow transplants, the current gene therapy methodologies, pitfalls of eradication strategies as well as future directions of the field.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1634193"},"PeriodicalIF":4.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The decision to purchase genome edited food products by Iranian consumers: theory of planned behavior as a social intervention tool.","authors":"Naser Valizadeh, Shobeir Karami","doi":"10.3389/fgeed.2025.1483510","DOIUrl":"10.3389/fgeed.2025.1483510","url":null,"abstract":"<p><p>The main aim of present study was to analyze the consumers' preferences about genome/gene-edited food products in Iran. For this purpose, an extended version of the theory of planned behavior was used as a social intervention tool. The theory of planned behavior was firstly extended using the introduction and new variable of trust in gene-edited products and perceived benefits of gene-edited food products, but in the next step, it was also analyzed statistically. To achieve the main objective of the research, a representative sample was selected from the population of purchasers of gene-edited products, and data were collected using a cross-sectional survey. The validity and reliability of the data collection tool was evaluated and confirmed using different quantitative and qualitative methods in the pilot stages and after the main survey. The results of structural equation modeling showed that the attitude towards gene-edited food products, perceived behavioral control, and the subjective norms of gene-edited products had positive and significant effects on the intention to purchase these products. The results of the study indicated that two newly introduced variables to the theory of planned behavior, namely, trust in gene-edited products and the perceived benefits of gene-edited products also had positive and significant effects on the intention to purchase these products. Based on the results, the framework employed and extended in this study can provide the basis for effective interventions to improve consumers' preference for gene-edited food products. Also, some practical suggestions were provided for policymakers, managers, and producers of these products.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1483510"},"PeriodicalIF":4.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of a multiplex CRISPR/Cas9 strategy for elimination of selection markers from transgenic plants.","authors":"Mohammed Rafi, Mohamed ElSiddig, Maitha Aldarmaki, Mariam Al Nuaimi, Suja George, Khaled M A Amiri","doi":"10.3389/fgeed.2025.1633104","DOIUrl":"10.3389/fgeed.2025.1633104","url":null,"abstract":"<p><p>Selectable marker genes (SMGs) are essential for identifying transgenic plants but raise concerns regarding biosafety, regulatory compliance, and public acceptance. In this study, we used a CRISPR/Cas9-based strategy to eliminate the SMG from transgenic tobacco plants. Leaf discs from plants carrying DsRED (SMG) and aminoglycoside phosphotransferase (gene of interest, GOI) were re-transformed with a CRISPR vector containing four gRNAs designed to target both flanking regions of the SMG cassette. Approximately 20% of the regenerated shoots exhibited loss of red fluorescence, and PCR and sequencing analyses confirmed that about half of these carried a smaller amplicon, indicating a successful SMG excision efficiency of around 10%. Mutation analysis further revealed the presence of small indels at gRNA target sites, in addition to the deletion of SMG cassette. Quantitative real-time PCR (qPCR) analysis confirmed the absence of DsRED expression in SMG-deleted lines, while the Cas9 and GOI remained actively expressed. The SMG-free plants displayed normal growth, flowering, and seed production, indicating CRISPR marker excision had no adverse effects on plant development and fertility. In addition, Cas9-free, marker-free transgenic plants were recovered through segregation in T1 generation. This approach is adaptable to various transgenic plant species and provides a practical solution for generating marker-free transgenic crops, thereby enhancing their acceptance and commercialization.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1633104"},"PeriodicalIF":5.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR-FMC: a dual-branch hybrid network for predicting CRISPR-Cas9 on-target activity.","authors":"Chuxuan Li, Jian Li, Quan Zou, Hailin Feng","doi":"10.3389/fgeed.2025.1643888","DOIUrl":"10.3389/fgeed.2025.1643888","url":null,"abstract":"<p><strong>Introduction: </strong>Accurately predicting the on-target activity of sgRNAs remains a challenge in CRISPR-Cas9 applications, due to the limited generalization of existing models across datasets, small-sample settings, and complex sequence contexts. Current methods often rely on shallow architectures or unimodal encodings, limiting their ability to capture the intricate dependencies underlying Cas9-mediated cleavage.</p><p><strong>Methods: </strong>We present CRISPR-FMC, a dual-branch hybrid neural network that integrates One-hot encoding with contextual embeddings from a pre-trained RNA-FM model. Multi-scale convolution (MSC), BiGRU, and Transformer blocks are employed to extract hierarchical sequence features, while a bidirectional cross-attention mechanism with a residual feedforward network enhances multimodal fusion and generalization.</p><p><strong>Results: </strong>Across nine public CRISPR-Cas9 datasets, CRISPR-FMC consistently outperforms existing baselines in both Spearman and Pearson correlation metrics, showing particularly strong performance under low-resource and cross-dataset conditions. Ablation experiments confirm the contribution of each module, and base substitution analysis reveals a pronounced sensitivity to the PAM-proximal region.</p><p><strong>Discussion: </strong>The PAM-proximal sensitivity aligns with established biological evidence, indicating the model's capacity to capture biologically relevant sequence determinants. These results demonstrate that CRISPR-FMC offers a robust and interpretable framework for sgRNA activity prediction across heterogeneous genomic contexts.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1643888"},"PeriodicalIF":4.4,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12426269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a homeolog-specific gene editing system in an evolutionary model for the study of polyploidy in nature.","authors":"Shengchen Shan, Michael T Pisias, Evgeny V Mavrodiev, Jonathan P Spoelhof, Bernard A Hauser, W Brad Barbazuk, Pamela S Soltis, Douglas E Soltis, Bing Yang","doi":"10.3389/fgeed.2025.1645542","DOIUrl":"10.3389/fgeed.2025.1645542","url":null,"abstract":"<p><p>Polyploidy, or whole-genome duplication (WGD), is a significant evolutionary force. Following allopolyploidy, duplicate gene copies (homeologs) have divergent evolutionary trajectories: some genes are preferentially retained in duplicate, while others tend to revert to single-copy status. Examining the effect of homeolog loss (i.e., changes in gene dosage) on associated phenotypes is essential for unraveling the genetic mechanisms underlying polyploid genome evolution. However, homeolog-specific editing has been demonstrated in only a few crop species and remains unexplored beyond agricultural applications. <i>Tragopogon</i> (Asteraceae) includes an evolutionary model system for studying the immediate consequences of polyploidy in nature. In this study, we developed a CRISPR-mediated homeolog-specific editing platform in allotetraploid <i>T. mirus</i>. Using the <i>MYB10</i> and <i>DFR</i> genes as examples, we successfully knocked out the targeted homeolog in <i>T. mirus</i> (4<i>x</i>) without editing the other homeolog (i.e., no off-target events). The editing efficiencies, defined as the percentage of plants with at least one allele of the targeted homeolog modified, were 35.7% and 45.5% for <i>MYB10</i> and <i>DFR</i>, respectively. Biallelic modification of the targeted homeolog occurred in the T₀ generation. These results demonstrate the robustness of homeolog-specific editing in polyploid <i>Tragopogon</i>, laying the foundation for future studies of genome evolution following WGD in nature.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1645542"},"PeriodicalIF":4.4,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12426060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prime editing using paired pegRNAs targeting NG- or NGG-PAM in rice.","authors":"Ayako Nishizawa-Yokoi, Keiko Iida, Akiko Mori, Seiichi Toki","doi":"10.3389/fgeed.2025.1550308","DOIUrl":"10.3389/fgeed.2025.1550308","url":null,"abstract":"<p><p>Prime editing (PE) enables precise genome modification, i.e., all 12 types of base substitution, as well as designed insertion and deletion. Previously, we developed an efficient PE system using a pair of engineered pegRNAs (epegRNAs), appending an RNA pseudoknot sequence to the 3'ends of pegRNAs to enhance stability and prevent degradation of the 3'extension. Using a wild-type nSpCas9-based PE system (PE-wt) recognizing an NGG-protospacer adjacent motif (PAM) in this approach, two NGG-PAMs (NGG and CCN) adjacent to the target site are required for targeting by paired pegRNAs; however, this is not the PAM configuration available at most target sites. Using an nSpCas9-NG variant recognizing NG-PAM in PE (PE-NG) can expand applicability. Here, we compare the PE efficiency of PE-wt with paired epegRNAs targeting a distal NGG-PAM <i>versus</i> PE-NG with paired epegRNAs targeting NG-PAMs adjacent to the target site. By introducing substitution and designated deletion mutations into target genes via PE-wt and PE-NG with paired epegRNAs, we demonstrated that PE-wt could edit the target site efficiently despite targeting the distal PAM site when either of the paired epegRNAs for PE-NG targets PGC-PAM. If epegRNAs for PE-NG are designed to recognize NGA and NGT-PAM, there is no significant difference in frequency between PE-NG and PE-wt. These findings indicate that PE efficiency via PE-NG is particularly low at the NGC-PAM in rice.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1550308"},"PeriodicalIF":4.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12426525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem cell and CRISPR/Cas9 gene editing technology in Alzheimer's disease therapy: from basic research to clinical innovation.","authors":"Cong He, Baojiang Chen, Ciai Yan, Xiaoqing Zhou","doi":"10.3389/fgeed.2025.1612868","DOIUrl":"10.3389/fgeed.2025.1612868","url":null,"abstract":"<p><p>Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by Aβ plaques, tau protein neuronal fiber tangles, and neuroinflammation, poses a significant global health problem, and current therapies focus on the symptoms rather than the cause. This paper gives a new multidimensional therapeutic form to AD treatment by exploring the integrated application of stem cell therapy and CRISPR/Cas9 gene editing technology. The study comprehensively dissected the roles of neural stem cells (NSCs), induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) in neural replacement, neuroinflammation modulation and neuroplasticity enhancement, and also explored the application of CRISPR/Cas9 in modifying the pathogenic variants of AD-related genes (APP, PSEN1 and PSEN2). The key findings suggest that gene-edited iPSCs can reduce abnormal Aβ and tau protein accumulation in AD models, improve cognitive function, and provide a platform for disease modeling and drug screening. Stem cell transplantation promotes neurogenesis and synaptic plasticity by secreting neurotrophic factors to improve the brain microenvironment. Despite the challenges of off-target effects, immune rejection, and long-term safety, the synergistic application of these two technologies offers a breakthrough solution for AD treatment. This paper highlights the translational potential of combining stem cells with gene editing technology, which is expected to drive clinical applications in the next 5-10 years. The integration of these advanced technologies not only addresses the limitations of current AD treatments, but also paves the way for a personalized medical approach that is expected to revolutionize the AD treatment landscape and bring new hope to patients worldwide.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"7 ","pages":"1612868"},"PeriodicalIF":4.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}