Current gene therapy最新文献

{"title":"Pathogens Association with Alzheimer Disease: Emerging Concepts and New Perspectives.","authors":"Uma Agarwal, Rajiv Kumar Tonk, Saroj Verma","doi":"10.2174/0115665232389348250722073721","DOIUrl":"10.2174/0115665232389348250722073721","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) represents a significant global health challenge, distinguished by a complex pathology that involves the accumulation of abnormal proteins in the brain, leading to neuronal loss and brain atrophy. Recent research has indicated a potential association between various pathogens and the development of AD, suggesting that infectious pathogens may play a role in its pathology. The study focuses on the exploration of pathogens linked to AD. It aims to enhance the understanding of the disease's etiopathogenesis, which refers to the causes and development of the condition. The findings from this analysis have the potential to contribute to improved diagnostic methods and treatment strategies for AD. Overall, the manuscript highlights the importance of exploring infectious pathogens relating to neurodegenerative disorders. This comprehensive literature review was conducted using databases such as PubMed and Scopus, focusing on research published up to March 2025..Articles were searched based on keywords related to reviews and research exploring the association/link between different pathogens and AD, emerging interventions, preventive strategies, and limitations in study design. This study indicates that various viruses, bacteria, and fungi are significant contributors to the condition, while parasites and prions play a lesser role. Notably, the variability in pathogen species among patients could provide insights into the evolution and severity of clinical symptoms associated with the disease. Additionally, some studies propose that after modification, certain fungi may actually reduce the amyloid burden in Alzheimer's patients. However, it is crucial to emphasize that there is currently no definitive evidence supporting the notion that treating infections alone can prevent or cure AD. The prevention and treatment of pathogens, including viruses, bacteria, and fungi, as well as infectious prions, may play a significant role in reducing the risk of AD. Effective management of these pathogens can help to control and prevent further damage in individuals who have already been diagnosed with AD. There is a pressing need for additional pre-clinical and clinical research to deepen the understanding of the pathophysiological connections between pathogens and AD.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"1-20"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741446","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":"Polysaccharide-Based Delivery Systems for CRISPR/Cas Gene Therapy: Overcoming Challenges and Advancing Pharmaceutical Solutions.","authors":"Deeksha Manchanda, Sunil Kumar, Manish Makhija","doi":"10.2174/0115665232369121250307075817","DOIUrl":"10.2174/0115665232369121250307075817","url":null,"abstract":"<p><p>The advent of CRISPR/Cas gene-editing technology has revolutionized molecular biology, offering unprecedented precision and potential in treating genetic disorders, cancers, and other complex diseases. However, for CRISPR/Cas to be truly effective in clinical settings, one of the most significant challenges lies in the delivery of the CRISPR components, including guide RNA (gRNA) and Cas protein, into specific cells or tissues. Safe, targeted, and efficient delivery remains a critical bottleneck. Viral vectors, lipid nanoparticles, and synthetic polymers have been explored, but they come with limitations, such as immunogenicity, toxicity, and limited delivery capacity. Polysaccharide-based delivery systems, with their natural origin, biocompatibility, and versatile chemical properties, offer a promising alternative that could address these delivery challenges while advancing the pharmaceutical applications of CRISPR/Cas gene therapy.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"1-4"},"PeriodicalIF":4.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604026","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":"A Comprehensive Review on Human Metapneumovirus.","authors":"Uma Agarwal, Swati Paliwal, Rajiv Kumar Tonk","doi":"10.2174/0115665232389869251014055641","DOIUrl":"https://doi.org/10.2174/0115665232389869251014055641","url":null,"abstract":"<p><strong>Background: </strong>Human metapneumovirus (HMPV) is a respiratory virus that presents symptoms similar to those of the common cold or influenza, including cough, nasal congestion, sore throat, fever, wheezing, and shortness of breath. The primary mode of transmission is through respiratory droplets from an infected person's cough or sneeze, as well as through contact with contaminated surfaces. HMPV was first recognized in 2001 and poses a significant public health concern, particularly affecting vulnerable groups like children, the elderly, and those with weakened immune systems. Its impact is notably severe in children under five years, contributing to rates of infant mortality. The main goal of the review article is to improve public health by gathering vital information on the human metapneumovirus (HMPV) and how it affects respiratory illnesses. It seeks to advance knowledge of these illnesses and methods of response.</p><p><strong>Methods: </strong>A thorough literature search was performed utilizing databases concentrating on studies published up to May 2025. The selection criteria were based on comprehensive prior research concerning human metapneumovirus on a global scale.</p><p><strong>Result: </strong>HMPV (Human Metapneumovirus) undergoes gradual mutations, leading to the emergence of new strains that are derived from previously circulating variants. Clinical features associated with different HMPV genotypes exhibit moderate variations, indicating some diversity in how the virus presents in patients. Notably, no significant seasonal trends have been observed in the incidence of HMPV infections, suggesting that the virus does not follow typical seasonal patterns seen with other respiratory viruses. In terms of severity, HMPV infections are generally less severe compared to those caused by Human Respiratory Syncytial Virus (HRSV). However, co-infection with both HMPV and RSV in young children has been linked to more severe illness than infections with either virus alone, highlighting the potential for compounded health risks in this demographic. Additionally, children hospitalized with HMPV are at an increased risk of developing acute kidney injury (AKI), with this risk correlating with age, independent of the severity of respiratory symptoms or existing comorbidities. Despite a significant increase in testing for respiratory viruses during the COVID-19 pandemic, the overall incidence of HMPV has remained stable, indicating that the pandemic did not lead to a surge in HMPV cases.</p><p><strong>Discussion: </strong>The evolutionary path of HMPV, marked by gradual mutations derived from earlier strains, restricts its ability to cause widespread pandemics. This view is supported by the lack of notable seasonal fluctuations and generally milder clinical impact compared to HRSV. Nonetheless, the rise in severity observed during co-infections highlights the need for accurate diagnosis and thorough monitoring. Many individuals' pre","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145480862","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":"Attenuated Salmonella Carrying IL-21-siRNA-CCR2 Co-expression Plasmid Enhances Anti-tumor Immune Response in Lung Cancer-bearing Mice.","authors":"Jing Li, Kun Li, Jinhua Yang, Mingyu Mo, Bingran Han, Jinwei Chen, Jiaxin Geng, Mengyu Lei, Pengfei Chen, Mingguang Shao, Hanyu Jiang, Tiesuo Zhao, Huijie Jia, Wei Wang","doi":"10.2174/0115665232407110251015103908","DOIUrl":"https://doi.org/10.2174/0115665232407110251015103908","url":null,"abstract":"<p><strong>Introduction: </strong>There is an urgent and ongoing need to develop effective therapeutic strategies for lung cancer. CCR2 is considered a valid target for lung cancer treatment. However, singletarget- oriented monotherapy frequently fails to yield satisfactory results, and multi-target therapy has become the current trend. IL-21 exerts anti-tumor effects across various cancers, including lung cancer. Whether the combination of CCR2-targeted therapy and IL-21 exerts a stronger anti-tumor effect remains to be verified.</p><p><strong>Methods: </strong>Mouse Lewis lung cancer cells and pre-constructed IL-21-siRNA-CCR2 plasmid were used. Annexin V-FITC, flow cytometry, Western blot, Ki67 IHC, immunofluorescence, and TUNEL assay were used to analyze apoptosis, immune cells, proteins, and proliferation.</p><p><strong>Results: </strong>Compared with single-agent treatments, combination treatment significantly inhibited CCR2 expression, enhanced IL-21 expression, and slowed tumor growth in mouse lung cancer tissues. Further analysis demonstrated that this treatment effectively increased the infiltration of CD4⁺ and CD8⁺ T lymphocytes in tumor tissues, elevated the proportion of M1 macrophages while reducing that of M2 macrophages, and notably increased the percentages of CD4+ T lymphocytes and NK cells in mouse spleens.</p><p><strong>Discussion: </strong>The combination treatment not only directly suppressed the proliferation of tumor cells but also enhanced the overall anti-tumor immune response in tumor-bearing mice. In subsequent studies, it will be further verified that the efficacy of this treatment is in a variety of tumor cell lines.</p><p><strong>Conclusion: </strong>The combination of IL-21 and CCR2 blockade exerts a synergistic anti-lung-cancer effect.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145376008","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":"Revolution of Traditional Chinese Medicine in Anticancer Therapy, Applications and Future Perspective.","authors":"Ashima Ahuja, Sonia Singh","doi":"10.2174/0115665232394088250930165852","DOIUrl":"https://doi.org/10.2174/0115665232394088250930165852","url":null,"abstract":"<p><p><p> Background: The battle against cancer has gained the interest of various researchers, scientists, pharmacologists, and pharmaceutical intervenors in China. Cancer is a leading cause of death worldwide, and the exploration of Traditional Chinese medicine plays an active role in modern medicine and patients with tumors. </p><p> Method: The literature search was done in PubMed, Web of Science, Scopus, PubChem, Google Scholar, SCI, and various online data sources. The review summarizes the pharmacology and applications of TCM as an adjuvant cancer therapeutic. </p><p> Results: More than 75% of cancer cases are treated using herbal remedies and alternative therapies like TCM in China. Researchers have focused on Western medicines for inhibiting cancer cell growth, apoptosis, and metastasis, with applications of TCM medicines in cancer patients. Furthermore, the complementary and alternative therapies used for cancer patients in China are helpful for cancer-fatigue patients with a combination of chemotherapy and radiotherapy. </p><p> Discussion: TCM is a promising strategy for researchers and provides a solid foundation for formulating future hypotheses for studies on TCM-based cancer therapy with fewer side effects and improving patient health. </p><p> Conclusion: TCM anticancer progress regulates immune responses and the role of natural killer cells, T and B cells, innate immunity, macrophages, and CD4+ lymphocytes. Additionally, chemopreventive measures in TCM nanotherapeutics shed light on underlying cancer mechanisms and cancer-suppressing genes, promoting the survival of cancer-affected patients in China. Further, it provides newer insights into the therapeutic effects of traditional Chinese medicine in controlling cancer cell growth, cancer stem cells, DNA methylation, apoptosis, and improving patient compliance, promoting health.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336639","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":"Precision Medicine: Design of Immune Inert Exosomes for Targeted Gene Delivery.","authors":"Fawzy A Saad","doi":"10.2174/0115665232409032250908114520","DOIUrl":"10.2174/0115665232409032250908114520","url":null,"abstract":"<p><p>Exosomes represent the smallest size among extracellular vesicles, which also include apoptotic bodies and microvesicles. Exosomes are natural nanocarriers that play a key role in intracellular communication, consisting of a hydrophobic lipid bilayer membrane and a hydrophilic core. The membrane compositions of exosomes are similar to those of the parent cells from which they are generated. Normally, the exosome membrane contains diacylglycerol, ceramide, cholesterol, and various surface proteins, including tetraspanins and Lamb2. Almost all cell types secrete exosomes into body fluids through exocytosis, including stem cells, epithelial cells, endothelial cells, immune cells, tumor cells, neurons, mast cells, oligodendrocytes, reticulocytes, macrophages, platelets, and astrocytes. Every cell type expresses a distinct type of exosomes carrying various bioactive molecules. Exosomes are major transporters of bioactive cargo, including enzymes, receptors, growth and transcription factors, nucleic acids, lipids, and other metabolites, which strongly affect the physiology of recipient cells. Exosomes are not only potent drug and gene delivery nanocarriers, but also have potential for disease diagnosis, tissue regeneration, and immunomodulation. Exosomes are present in various body fluids, including plasma, serum, saliva, milk, nasal secretions, urine, amniotic fluid, semen, and cerebrospinal fluid, among others. Stem cell-made exosomes are potential natural therapeutics, which is due to their rejuvenating cargo and ability to cross biological barriers. However, natural exosomes' inefficient cargo transfer and short lifespan in the bloodstream have hindered their progress in therapeutic interventions. Genetic engineering of the parent cell allows for loading specific therapeutic cargo into the lumen of newly generated exosomes and/or displaying certain homing peptides or ligands at their surface, leading to extension of their lifespan and precise delivery to specific organs or tissues. This minireview explores the creation of designer exosomes through parent cell engineering and their utilization for guiding the delivery of tailored therapeutic cargo to specific organs while evading the host's innate immune response.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198574","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":"Advancing Antibacterial Strategies: CRISPR-Phage-Mediated Gene Therapy Targeting Bacterial Resistance Genes.","authors":"Arvind Kumar Patel, Neha Singh, Neetu Sachan, Phool Chandra","doi":"10.2174/0115665232417037250916112841","DOIUrl":"https://doi.org/10.2174/0115665232417037250916112841","url":null,"abstract":"<p><p>One of the most significant issues facing the world today is antibiotic resistance, which makes it increasingly difficult to treat bacterial infections. Regular antibiotics no longer work against many bacteria, affecting millions of people. A novel approach known as CRISPR-phage therapy may be beneficial. This technique introduces a technology called CRISPR into resistant bacteria using bacteriophages. The genes that cause bacteria to become resistant to antibiotics can be identified and cut using CRISPR. This enables antibiotics to function by inhibiting the bacteria. This approach is highly precise, unlike conventional antibiotics, so it doesn't damage our bodies' beneficial bacteria. Preliminary studies and limited clinical trials suggest that this technique can effectively target drug-resistant bacteria such as Klebsiella pneumoniae and Methicillinresistant Staphylococcus aureus (MRSA). However, challenges in phage engineering, host delivery, and the growing threat of bacterial CRISPR resistance demand urgent and strategic innovation. Our perspective underscores that without proactive resolution of these hurdles, the current hopefulness could disappear. Looking ahead, integrating next-generation Cas effectors, non-DSB editors, and resistance monitoring frameworks could transform CRISPR-phage systems from an experimental novelty into a clinical mainstay. This shift will require not only scientific ingenuity but also coordinated advances in regulatory, translational, and manufacturing efforts.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130079","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":"A Comprehensive Review of Genetic Risk Factors for Alzheimer's Disease Development.","authors":"Aniket Kakkar, Harpreet Singh, Amit Anand, Arun Kumar Mishra, Arvind Kumar, Hitesh Chopra","doi":"10.2174/0115665232397101250916050247","DOIUrl":"https://doi.org/10.2174/0115665232397101250916050247","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) is a progressive neurodegenerative disorder with a complex genetic basis involving both rare mutations and common variants. This review provides a comprehensive synthesis of established and emerging genetic risk factors implicated in AD pathogenesis. Mendelian forms are strongly associated with mutations in APP, PSEN1, and PSEN2, whereas the APOE ε4 allele remains the most robust genetic risk factor for late-onset AD. Recent Genome- Wide Association Studies (GWAS) have uncovered additional susceptibility loci, including TREM2, CLU, ABCA7, and SORL1, which reflect diverse biological pathways such as amyloid metabolism, lipid regulation, and immune response. The review also highlights the roles of epigenetic mechanisms such as DNA methylation and histone modifications, as well as geneenvironment interactions in modulating disease risk and progression. Although substantial progress has been made in identifying genetic contributors, translating these findings into clinical applications remains challenging. This article underscores the need for integrative, multi-omic approaches and population-diverse studies to enhance risk prediction and enable personalized interventions for prevention and therapy in AD.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130145","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":"Synergistic Antiproliferative Effects of EGCG and Myricetin on Cervical Cancer Biomarkers in ME180 and SiHa Cell Lines.","authors":"Kaviyaprabha Rangaraj, Miji Thandaserry Vasudevan, Suseela Rangaraj, Rachana Kumar, Sridhar Muthusami, Tahani Awad Alahmadi, Arunachalam Chinnathambi, Palanisamy Arulselvan, Chaiyavat Chaiyasut, Muruganantham Bharathi","doi":"10.2174/0115665232363374250901071820","DOIUrl":"https://doi.org/10.2174/0115665232363374250901071820","url":null,"abstract":"<p><strong>Introduction: </strong>Identifying potential biomarkers for the detection, diagnosis, and monitoring of cervical cancer (CC) constitutes a key area for future research.</p><p><strong>Methods: </strong>Differentially expressed genes (DEGs) and survival-associated DEGs (SDEGs) were identified using the GEPIA2 database through the TCGA-CESC dataset. The 3D structures of target proteins were predicted using trRosetta and validated via SAVES v6.0. Phytocompounds were retrieved from the PubChem database, and docking studies were performed using AutoDock Vina. The miRNAs regulating HK2 and MAP7 were also predicted by implementing miRNetv2.0 and the CancerMIRNome database. Finally, the anticancer activity of these compounds was validated individually and in combination using the ME180 and SiHa CC cell lines.</p><p><strong>Results: </strong>The present study identified the top five most hazardous novel biomarkers through DEGs (5763) and SDEGs (500) (P-value ≤ 0.05). The phytocompounds EGCG and myricetin interacted with HK2 with binding affinities of -8.3 and -8.1 kcal/mol and RMSDs of 1.369Å and 1.452Å, respectively. Similarly, EGCG (-9.1 kcal/mol) and myricetin (-7.9 kcal/mol), with the RMSD of 1.682Å and 1.148Å, showed strong bonding with the MAP7. EGCG and myricetin treatment synergistically inhibited ME180 (IC50 = 63.49μM) and SiHa (IC50 = 81.54μM) cell-proliferation. miRNAs regulating HK2 and MAP7 were identified, including hsa-mir-484 (HK2) and hsa-mir-17-5p, hsa-mir-93-5p, hsa-mir-106b-5p, among others (MAP7).</p><p><strong>Discussion: </strong>EGCG and myricetin, in combination, showed a synergistic effect on the ME180 cell line compared to the SiHa cell line.</p><p><strong>Conclusion: </strong>More in vitro and cell- and patient-derived xenograft models studies are needed to support the synergistic effect of EGCG and myricetin.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111939","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":"Advances in Gene Therapy Clinical Trials for Hemophilia Care.","authors":"Amita Joshi Rana, Md Sadique Hussain, Vikas Jakhmola, Gaurav Gupta","doi":"10.2174/0115665232413510250904105956","DOIUrl":"10.2174/0115665232413510250904105956","url":null,"abstract":"<p><p>Gene therapy has revolutionized the therapeutic landscape for hemophilia A and B, offering the prospect for persistent endogenous production of coagulation factors VIII and IX. Recent advances in adeno-associated virus (AAV)-mediated gene transfer, particularly the approvals of valoctocogene roxaparvovec (Roctavian) and etranacogene dezaparvovec (Hemgenix), mark significant milestones in hemophilia care. This mini-review synthesizes emerging clinical data from phase I-III trials published between 2022 and 2025, emphasizing efficacy, durability, and immunogenicity profiles of leading AAV-based therapies. Innovations in vector design, such as liverspecific promoters, codon-optimized constructs, and novel capsids (e.g., AAVhu37, AAVrh10, AAV-Spark100), have improved transgene expression and expanded eligibility. Despite notable success, challenges persist, including immune-mediated transaminitis, declining factor activity over time, particularly in hemophilia A, and limitations posed by preexisting neutralizing antibodies. Additionally, CRISPR-Cas9 and non-viral delivery systems are emerging as complementary strategies, potentially enhancing therapeutic precision and overcoming AAV-related barriers. The review also addresses the critical need for equitable access and scalable production models to ensure global availability of gene therapies. With ongoing innovation and multidisciplinary collaboration, gene therapy is poised to transition from experimental intervention to mainstream curative care in hemophilia and other hematologic diseases.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014069","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}