Current gene therapy最新文献

{"title":"Effect of Source and Time of Collection on rAAV9 Production Yield and Quality: A Comparative Bioprocess Analysis.","authors":"Kadarkarai Raj Rajendran, Sharath Babu G R, Ravikiran Macherla, Arkasubhra Ghosh","doi":"10.2174/0115665232489928260716120134","DOIUrl":"https://doi.org/10.2174/0115665232489928260716120134","url":null,"abstract":"<p><strong>Introduction: </strong>A comprehensive analysis of Critical Quality Attributes (CQAs) is crucial for extended culture conditions across sources and time points.</p><p><strong>Methods: </strong>The rAAV9-eGFP vectors were produced. Further, collected lysates and culture supernatants (sources) were purified by affinity chromatography (AC) at two time points (72 and 120 hours). Detailed CQA analysis, including vector genome titer, capsid protein abundance, purity, aggregates, and transduction efficiency, was conducted.</p><p><strong>Results: </strong>The viral titer yield from the 72-h media supernatant was 1.29×1013 ± 7.62×1011 vgc, whereas the lysate yielded 5.28 × 10¹² ± 7.64×1011 vgc. At the 120-h harvest, the supernatant again yielded 7.22 × 10¹² ± 8.97 × 10¹¹ vgc, while the lysate yielded 1.39 × 10¹¹ ± 5.25 × 1010 vgc. ACbased purification showed the absence of degraded capsid proteins, with no detectable host-cell protein contamination across time points. Notably, the SEC revealed pronounced higher-order dimers in 120-h (23% & 55%) lysate-derived vectors purified by AC and CsCl. Transduction efficiency was significantly reduced in the 120-h lysate-purified vectors compared with 72-h lysate (p=0.001) and corresponding 72- and 120-h media supernatants (p=0.004 and p=0.001, respectively).</p><p><strong>Discussion: </strong>Substantial variation was observed in total vector yield, with media supernatants consistently yielding higher titers than lysates at both time points. Future studies should focus on process parameters to suppress dimer formation under extended culture conditions and elucidate the impairment of transduction in late-harvest, lysate-derived AAV particles.</p><p><strong>Conclusion: </strong>The current study established rAAV9 media supernatant harvested at 72-hr and 120-hr as a preferred source selection for improving yield, purity, and potency during scale-up processes.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SMART Nanocarriers for siRNA Delivery: Stimuli-Responsive Platforms for Targeted Gene Silencing.","authors":"Nagashree D, Manisha S Jain, Harshitha K S, Sania Hermain, Nimbagal Raghavendra Naveen","doi":"10.2174/0115665232501139260924083439","DOIUrl":"https://doi.org/10.2174/0115665232501139260924083439","url":null,"abstract":"<p><p>Despite the remarkable specificity of small interfering RNA (siRNA)-based treatments for gene silencing, biological limitations like poor stability, rapid systemic clearance, immunogenicity, and inefficient intracellular delivery hinder their clinical translation. A promising strategy for overcoming these challenges and enabling precise, site-specific gene silencing is the use of SMART nanocarriers, including stimuli-responsive, adaptable, and multifunctional delivery platforms. Controlled siRNA release, enhanced cellular uptake, and effective endosomal escape are enabled by these novel nanocarriers' ability to respond dynamically to exogenous triggers such as light, ultrasound, and magnetic fields as well as endogenous stimuli such as pH gradients, redox potential, enzymatic activity, and hypoxia. Recent advances have combined rational material design, surface functionalization with targeted ligands, and modular architectures to gain spatiotemporal control over gene silencing while limiting unintended targets and systemic toxicity. This study examines the critical design concepts, fabrication methodologies, and molecular pathways governing SMART nanocarrier-mediated siRNA distribution, with a focus on polymeric, lipid-based, inorganic, and bioinspired platforms. The article highlights key preclinical and emerging clinical breakthroughs, as well as issues with scalability, repeatability, immunocompatibility, and regulatory translation. This review emphasizes the critical significance of stimulus-responsive nanocarriers in developing siRNA treatments towards precision medicine applications in oncology, neurological disorders, and inflammatory illnesses by consolidating recent studies and future prospects.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA Therapeutics in Cancer: Revisiting the Promise and Understanding the Limitations of Clinical Translation.","authors":"Linh T T Le","doi":"10.2174/0115665232513137260921053855","DOIUrl":"https://doi.org/10.2174/0115665232513137260921053855","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) have emerged as promising therapeutic agents in cancer because of their ability to simultaneously regulate multiple oncogenic pathways and gene networks. Early preclinical studies demonstrated substantial anti-tumor activity, generating considerable enthusiasm for the rapid clinical translation of miRNA-based therapeutics. However, despite strong mechanistic rationale and encouraging experimental results, the successful clinical application of miRNA therapeutics has remained limited. To date, only a small number of miRNA-based candidates have entered clinical trials, and none have achieved regulatory approval for cancer treatment. This review summarizes advances in miRNA-based cancer therapeutics and discusses the major factors limiting their translation into clinical practice. We discuss current strategies for miRNA restoration and miRNA inhibition, together with advances in delivery technologies, including lipid nanoparticles, polymer-based carriers, viral vectors, exosomes, and ligand-conjugated systems. Furthermore, evidence from preclinical and clinical studies to assess the efficacy, safety, and translational potential of these approaches have been summarized. Special emphasis was placed on the biological and technical barriers which continue to restrict the clinical success, including inefficient and nonspecific delivery, off-target effects, immune-related toxicities, tumor heterogeneity, and the contextdependent nature of miRNA function within complex tumor microenvironments. Overall, the available evidence suggests that miRNA-based therapeutics continues to hold a significant promise in oncology. Although substantial biological and technical challenges still remains to be addressed to achieve their widespread clinical implementation.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene-Driven Precision Medicine: Enhancing Biomarker Identification for Personalized Therapy.","authors":"Mohamed Abbas, Abdallah Saleh, Hashim Elshafie, Mohamad Yahya H Al-Shamri, Suresh Babu Changalasetty, Azath Mubarakali","doi":"10.2174/0115665232398321251118011107","DOIUrl":"https://doi.org/10.2174/0115665232398321251118011107","url":null,"abstract":"<p><p>Transformative advances in biomarker science are reshaping the landscape of precision medicine, offering powerful tools for early disease detection, accurate prognostication, and individualized therapeutic design. This review synthesizes recent progress in biomarker discovery, classification, and clinical application across multiple medical domains, emphasizing their pivotal role in enhancing diagnostic precision and personalizing treatment strategies. Central to these advances is the integration of next-generation sequencing, advanced mass spectrometry, artificial intelligence, and multi-omics technologies, which collectively strengthen biomarker reliability and reproducibility. The review also explores the contributions of non-coding RNAs, tumor microenvironment dynamics, and immune-inflammatory pathways in constructing disease-specific biomarker profiles. In fields such as oncology, neurology, and infectious diseases, biomarker-driven approaches are transforming drug development and clinical decision-making. However, challenges such as biological variability, lack of standardization, and ethical concerns necessitate coordinated, multidisciplinary solutions. Emerging innovations, including machine learning-driven analytics, single-cell technologies, and wearable biosensors, signal a shift toward more dynamic diagnostics and adaptive interventions. By charting the current and emerging biomarker landscape, this review underscores the shift toward patient-centric care models. It concludes by highlighting the importance of cross-sector collaboration to accelerate the clinical translation of biomarker innovations, ultimately advancing health equity and improving global healthcare outcomes.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of CDKN1A as a Candidate Therapeutic Target in Peripheral Artery Disease Progression: Integrative Multi-omics and Mendelian Randomization Study.","authors":"Shengquan Chen, Haotian Zhu, Chuan Zhang, Huarong Xie, Yongkang Li, Shujing Zhang, Shaoying Lu, Jun Feng, Jichang Wang","doi":"10.2174/0115665232507240260910050841","DOIUrl":"https://doi.org/10.2174/0115665232507240260910050841","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Therapeutic strategies for advanced Peripheral Artery Disease (PAD), including angiogenic gene therapy trials, have yielded limited clinical benefit, partly because target selection has relied on empirical biological reasoning rather than genetic causal evidence. Since the progression from Intermittent Claudication (IC) to Critical Limb Ischemia (CLI) represents a critical stage of PAD progression, identifying genetically supported causal targets underlying this transition is essential for developing effective molecular interventions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;An integrative analytical framework was applied, combining bulk transcriptomics, Weighted Gene Co-expression Network Analysis (WGCNA), differential expression analysis, Protein- Protein Interaction (PPI) network construction, and machine-learning-based feature selection. Candidate genes were further characterized using single-cell RNA sequencing (scRNA-seq) and validated in an in vivo murine Hindlimb Ischemia model (HLI). Immune infiltration was assessed by CIBERSORT. Genetic causal evidence was obtained through GWAS colocalization and bidirectional Mendelian Randomization (MR). Computational gene perturbation analysis was performed to predict downstream transcriptional consequences. Phenome-Wide Association Study (PheWAS) and drug-gene interaction analyses were conducted to explore pleiotropy and therapeutic relevance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Multi-stage screening consistently identified CDKN1A as a central hub gene associated with ischemic severity. At single-cell resolution, CDKN1A was broadly upregulated across multiple cell types within the ischemic niche and positively correlated with M2 macrophage infiltration. This ischemia-dependent induction was confirmed at the protein level in vivo. Integrative genetic analyses, including GWAS colocalization (PP.H4 = 0.90) and bidirectional MR, provided evidence supporting a causal link between genetically predicted CDKN1A expression and PAD risk, with no evidence of reverse causation. Computational gene perturbation analysis identified downstream transcriptional programs associated with extracellular matrix remodeling, TGF-beta signaling, and angiogenesis. PheWAS showed no genome-wide significant associations across 19 phenotype categories, and drug-gene interaction analysis identified resveratrol as a candidate modulator.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;The current findings indicate that CDKN1A-mediated stress response represents a key mechanism in PAD progression, linking ischemic injury to maladaptive remodeling and supporting its relevance as a genetically supported candidate therapeutic target in PAD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Our findings provide convergent transcriptomic, cellular, and genetic evidence supporting CDKN1A as a genetically supported candidate causal target associated with PAD progression. These results suggest that CDKN1A-mediated cell-cycle arrest and associated s","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PSKH1: A Promising Therapeutic Target in Prostate Cancer, Mechanisms and Potential Interventions.","authors":"Vanktesh Kumar, Nancy Saini, Pankaj Wadhwa","doi":"10.2174/0115665232472718260908102938","DOIUrl":"https://doi.org/10.2174/0115665232472718260908102938","url":null,"abstract":"<p><p>Cancer of the prostate is an important issue on a global scale, and therefore the identification of targets to support the development of therapy for this cancer should be a priority, particularly given the rise in cases of advanced prostate cancer and of patients who have developed resistance to the current standard of care therapies. Protein kinases have been the most heavily researched and targeted class of drug candidates in oncology, and they play a pivotal role in cellular signaling. This review examines Protein Serine Kinase H1 (PSKH1), which is an example of a member of the 'dark kinome' that is not extensively studied. PSKH1 recently emerged as a major component of cancer development. Functional RNAi screens demonstrated that PSKH1 enhances proliferation in both androgen-dependent and castration-resistant prostate cancer models. PSKH1's mechanism of action is distinct, as it has two major regulatory nodes: Calcium-dependent phosphorylation by Calmodulin activates it, and Reticulocalbin-3 inhibits PSKH1 through protein-protein interactions. Additionally, PSKH1 activates several pro-survivals signaling pathways (such as p38 MAPK) and regulates alternative splicing of pre-mRNAs in cancer. This review will summarize recent studies relating to the importance of PSKH1 as a potential therapeutic target for prostate cancer. This study discusses PSKH1's general biochemistry, its association with cancer, and the signaling pathways it regulates. Moreover, this study presents a multi-pronged approach linking how it can be inhibited therapeutically, including ATP-competitive and allosteric inhibition, protein- protein interaction displacement, protein degraders (PROTACs), and nucleic acid therapeutics. This study proposes that PSKH1 inhibition represents a novel treatment opportunity to simultaneously interfere with multiple oncogenic pathways and is expected to circumvent resistance and potentiate other treatments. Lastly, this study presents a roadmap of future studies to clinically validate PSKH1 and fast-track the discovery of first-in-class inhibitors of this novel target.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends and Hotspots in the Convergence of Artificial Intelligence and Cell and Gene Therapy: A Patent Analysis.","authors":"Hongmei Yuan, Yuandong He, Cuiyan Wang, Baijun Liu","doi":"10.2174/0115665232515473260910071847","DOIUrl":"https://doi.org/10.2174/0115665232515473260910071847","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The convergence of Artificial Intelligence (AI) and Cell and Gene Therapy (CGT) represents a frontier in next-generation therapeutic innovation, yet the structural patterns of technology convergence within this interdisciplinary field remain poorly characterized. This study aims to develop a computational framework for predicting which technology linkages are most likely to strengthen within this convergence landscape, thereby providing a data-driven basis for R&D resource allocation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;Global patent data in the AI-CGT field were collected to construct a time-series heterogeneous network in which International Patent Classification (IPC) codes serve as technology nodes and individual patents as knowledge nodes, capturing co-occurrence, affiliation, and citation relationships among technologies. At the macro forecasting level, a Temporal Heterogeneous Graph Neural Network (THGNN) was employed for link prediction. The model aggregated multi-hop neighbor information through meta-paths and leveraged Long Short-Term Memory (LSTM) networks to capture technological evolution dynamics, with the aim of identifying IPC pairs with the highest future association weights. At the micro-analysis level, Latent Dirichlet Allocation (LDA) topic modeling was applied to patents associated with the core IPC pairs. The optimal number of topics was determined by combining perplexity curves with inter-topic distance visualization to reveal the key technological content of these IPC associations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Result: &lt;/strong&gt;The temporal heterogeneous graph neural network model achieved an Area Under the Curve (AUC) of 0.7539, Average Precision (AP) of 0.7862, and F1 score of 0.7568 for link prediction. Based on this model, multiple high-confidence convergence pathways were identified, among which the predicted potential for association strengthening between biochemical detection (C12Q1) and neural networks (G06N3) and between genetic engineering (C12N15) and neural networks (G06N3) received the highest prediction scores (0.89 and 0.80, respectively), suggesting that these pairs are likely to constitute the primary axes of technology convergence in this field.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;The two major convergence directions identified above correspond to the core bottlenecks in CGT clinical translation-namely, the precision and safety of gene editing, and the quality control and efficacy monitoring of therapeutic products. These findings reveal a patent-based convergence landscape in which AI-related patent classifications increasingly co-occur with both detection and therapeutic methods, indicating a trend of AI integration across the diagnostic-totherapeutic continuum at the level of patent disclosures. The identified convergence directions are computational predictions based on patent co-occurrence patterns and carry inherent uncertainty; they represent technology convergence signals rather than c","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence-Driven Gene Delivery Systems in Dementia: A Comprehensive Review of Mechanisms, Tools, and Therapeutic Strategies.","authors":"Ankita Wal, Manmohan Shukla, Pranay Wal, Saumya Singh, Brijesh Chaurasia, Hanish Singh Jayasingh Chellammal, Amin Gasmi","doi":"10.2174/0115665232436545260906074748","DOIUrl":"https://doi.org/10.2174/0115665232436545260906074748","url":null,"abstract":"<p><strong>Introduction/objective: </strong>The progressive nature of dementia is represented by a reduction in two or more cognitive functions, including language, memory, executive and visuospatial functioning, personality, and behavior. Only symptoms can be alleviated by traditional medication therapies. A strategy that shows promise for focused and customized interventions is gene therapy, especially when combined with artificial intelligence (AI).This review investigates the integration of AI with gene delivery technologies to enhance the accuracy, effectiveness, and personalization of dementia therapies.</p><p><strong>Method: </strong>PRISMA guidelines were followed in conducting a systematic review. A literature search for English-language articles published between 2012 and 2026 was conducted using PubMed, Scopus, and Google Scholar. Peer-reviewed original research, computational studies, or reviews; attention to AI in the context of gene delivery in dementia; and pertinence to biological mechanisms or therapeutic approaches were the inclusion criteria. Non-English papers, conference abstracts, letters, editorials, and research unrelated to gene delivery or dementia were among the exclusion criteria. The full texts, abstracts, and titles were vetted by two separate reviewers. Discussions or seeking advice from a third reviewer were used to settle disagreements.</p><p><strong>Results: </strong>AI has proven to be very helpful in predicting therapeutic targets, optimizing gene vectors, and customizing dementia treatment plans. Using machine learning and deep learning approaches, it also makes gene-target prediction, nanocarrier optimization, and post-treatment monitoring easier. These methods improve vector design, find biomarkers, and decode complex genomic data. Precision gene delivery across the blood-brain barrier is now possible because to integration with (Clustered Regularly Interspaced Short Palindromic repeat) CRISPR/Cas9, adeno-associated virus vectors, and lipid nanoparticles, which has increased transfection efficiency and decreased cytotoxicity.</p><p><strong>Conclusion: </strong>Precision medicine is becoming possible because of AI frameworks that integrate neuroimaging, multi-omics data, and patient-specific genomic profiles. Notwithstanding the potential, there are still issues including data security, ethical dilemmas, translational barriers, and legal limitations.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prime Editing and Its Delivery: Recent Advances in Gene Correction for Genetic Diseases.","authors":"Shuran Zhang, Le Chang, Yamin Kong, Wenming Huang, Jinman Zhang, Baosheng Zhu, Ying Chan","doi":"10.2174/0115665232491924260907063026","DOIUrl":"https://doi.org/10.2174/0115665232491924260907063026","url":null,"abstract":"<p><p>Prime editing (PE), as a transformative genome-editing technology, overcomes many of the limitations of CRISPR-Cas9, particularly by enabling high-fidelity base conversions independent of double-strand breaks (DSBs). This unique mechanism significantly reduces unintended insertions, deletions, and chromosomal rearrangements, positioning PE as a safer and more precise tool for therapeutic gene correction. Recently, the world's first FDA-approved PE clinical trial (PM359 for chronic granulomatous disease) was officially launched, representing a major milestone in the field and highlighting the growing clinical translational potential of PE for treating human genetic disorders. Since the introduction of PE technology, extensive research efforts have been devoted to improving its gene correction efficiency, expanding the editing window, broadening target-site compatibility, reducing the size of the editing protein, and optimizing in vivo delivery vector systems. This review systematically summarizes the key improvements and evolutionary progress in the prime editor design and its updated delivery systems, with a particular focus on innovative modifications that have successfully overcome technical barriers. This study also highlights recent advances in engineered PE variants and their derivative systems, which have collectively expanded the scope and precision of PE-mediated gene correction. Additionally, this study critically discusses the remaining limitations and challenges associated with its application.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanocarrier-Mediated Nucleic Acid Therapy in Non-Small Cell Lung Cancer: Converging Delivery Barriers, Resistance Reversal, and Clinical Translation.","authors":"Yu Haitao, Yan Jianqin, Gao Song, Qiao Weili, Wang Maolong","doi":"10.2174/0115665232473217260821092300","DOIUrl":"https://doi.org/10.2174/0115665232473217260821092300","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer remains a leading cause of cancer-related mortality worldwide, and non-small cell lung cancer (NSCLC) is the major histological subtype. Although chemotherapy, molecular targeted therapy, and immune checkpoint blockade have improved outcomes in selected patients, therapeutic resistance, tumor heterogeneity, systemic toxicity, and limited responsiveness still restrict durable clinical benefit. This review critically evaluates nanocarrier-mediated gene delivery for gene regulation, combination therapy, and resistance reversal in NSCLC.</p><p><strong>Methods: </strong>As a narrative review, this article integrates studies on nucleic acid nanomedicine relevant to NSCLC using a barrier-payload-resistance-translation framework, focusing on payload compatibility, intracellular trafficking, endosomal escape, immune safety, pharmacokinetics, biodistribution, and translational feasibility.</p><p><strong>Results: </strong>Small interfering RNA (siRNA), microRNA (miRNA), antisense oligonucleotides (ASOs), and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) systems can modulate oncogenic signaling, resistance-associated pathways, and the tumor immune microenvironment. However, effective delivery requires overcoming nuclease degradation, mononuclear phagocyte clearance, heterogeneous tumor accumulation, stromal barriers, inefficient cellular uptake, insufficient endosomal escape, immune activation, and uncertain pharmacokinetic and biodistribution profiles.</p><p><strong>Discussion: </strong>This review discusses lipid-based, polymeric, inorganic, bio-derived, and viral systems according to payload compatibility, intracellular delivery requirements, safety, and clinical feasibility. Particular emphasis is placed on resistance mechanisms beyond classical multidrug efflux, including epithelial-mesenchymal transition (EMT), cancer stem cell-associated resistance, DNA damage repair, bypass activation of targeted therapy pathways, immune escape, and metabolic reprogramming.</p><p><strong>Conclusion: </strong>Future nanocarrier-based gene therapy for NSCLC should move beyond material innovation toward barrier-informed, resistance-matched, biomarker-guided, and clinically scalable precision nanomedicine.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}