Current Gene Therapy[JOURNAL]
Sun
200 papers
Recent Advances on RNA-Based Molecular Therapies for Tumour Cell Targeting.
Sharma N, Bhati A, Shah K … +1 more , Dewangan HK
Curr Gene Ther · 2026 Jan · PMID 41508958 · Publisher ↗
Anticancer drug therapy primarily focuses on exploiting genetic alterations that already exist in tumour cells. This understanding can help to utilize the conventional therapeutics with much better results. The identific...
Anticancer drug therapy primarily focuses on exploiting genetic alterations that already exist in tumour cells. This understanding can help to utilize the conventional therapeutics with much better results. The identification of genes whose loss of function alters the tumor growth, enhances the cytotoxic characterises or leads to enhancement in the apoptotic nature of tumor cells can be done by the use of Loss-of-function genetic screens. In this review, we summarise RNAbased therapies, including mechanisms of action, clinical applications, and advancements with nanoparticles and artificial intelligence for tumor targeting in cancer. Many techniques are being explored for the promotion of RNA tracking of intracellular activities and production of metabolic stability. The emerging role of RNA in diagnosis and treatment has been a topic of discussion in the field of medical sciences. Different types of RNAs, such as small interfering RNA (siRNA), microRNA (miRNA), etc and Exosomes RNA delivery are being used for employment as the delivery system, which are considered as the therapeutic targeting system. 56 mRNA drugs have been in the pipeline for entering the clinical pipeline and nearly 108 oligonucleotide drugs are entering the clinical pipeline worldwide, including ASOs, siRNAs, aptamers and miRNAs. These different types, although they assist each other in their proper working and still function in very different ways. Most of these are under investigation, while some have been approved for clinical use. RNA-based therapies hold great potential for cancer treatment due to their specificity and adaptability. Continued research into improving delivery methods, reducing side effects, and exploring new RNA targets will be crucial in advancing these therapies to clinical practice.
Identifying Key Epigenetic Modification-Related Genes for Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma and Cellular Validation.
Zhang H, Li J, Xu H … +3 more , Zhang S, Lu Y, Feng S
Curr Gene Ther · 2026 · PMID 41293945 · Publisher ↗
INTRODUCTION: Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC) is a highly prevalent female malignancy. As the epigenomic characteristics of immune cells and cancer cells can serve as predictive in...
INTRODUCTION: Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC) is a highly prevalent female malignancy. As the epigenomic characteristics of immune cells and cancer cells can serve as predictive indicators for the response to cancer immunotherapy, analysis of epigenetically modified genes (EpiGenes) could contribute to CESC treatment. METHODS: The ssGSEA algorithm was employed to compute EpiGenes scores. Core genes that exhibited significant module association and a close correlation with EpiGenes scores were identified via the WGCNA package. Univariate Cox proportional hazards regression was performed on the core genes using the survival package, followed by gene set reduction via LASSO Cox regression. Ultimately, key genes were determined through multivariate Cox regression to establish a RiskScore model. Further, the optimal risk cutoff was determined using the survminer package to stratify CESC patients into high- and low-risk subgroups. For enrichment analysis, clusterProfiler and GSEA were utilized. Immune infiltration across risk groups was evaluated via ssGSEA, the MCPcounter algorithm, and the ESTIMATE algorithm. TIDE was employed to compare immunotherapeutic responses between the risk groups, while the pRRophetic software was utilized to predict patients' chemotherapeutic drug sensitivity. The biomarkers identified were validated by performing in vitro experiments. RESULTS: , and were identified by computational analyses as the key genes for CESC and further validated through experiments. Pathway enrichment analysis revealed predominant enrichment in immune-related pathways in the high-risk group, whereas the low-risk group was more enriched in energy and metabolic pathways. A significant negative correlation was observed between CD8+ T cell abundance and RiskScore, with higher ESTIMATEScores and StromalScores in high-risk patients. Notably, the high-risk group also demonstrated lower potential sensitivity to immunotherapy but more active responsiveness to a broader spectrum of chemotherapeutic agents. DISCUSSION: Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that module genes are significantly enriched in cell cycle regulatory pathways, and these genes, in conjunction with Human Papillomavirus (HPV) infection-induced cell cycle dysregulation, jointly participate in CESC pathogenesis, providing a mechanistic basis for understanding the disease. CONCLUSION: This study provided novel theoretical evidence for immunotherapy and chemotherapy selection in the management of CESC.
A Comprehensive Review on Human Metapneumovirus.
Agarwal U, Paliwal S, Tonk RK
Curr Gene Ther · 2025 Nov · PMID 41208068 · Publisher ↗
BACKGROUND: 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 b...
BACKGROUND: 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. METHODS: 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. RESULT: 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. DISCUSSION: 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-existing immunity may help lessen the effects of new HMPV infections, indicating that targeted vaccines or immune-boosting approaches could be beneficial. Additionally, the surprising link between HMPV and acute kidney injury, particularly in older children, calls for more research into its non-respiratory complications. The stable infection rates during the pandemic, despite increased testing efforts, suggest that the virus's transmission patterns remain consistent. CONCLUSION: HMPV is less researched compared to other respiratory viruses, raising concerns about its management. The necessity of routine HMPV testing is highlighted alongside the need for further research to improve treatment and prevention strategies. Despite advancements in understanding the virus, significant challenges remain in deciphering its mechanisms and developing effective therapeutics. There is an urgent need for targeted antivirals and vaccines for at-risk populations, along with comprehensive data on HMPV-related diseases to guide future research and interventions.
Foxp3 Tregs Promote M2 Macrophage Polarization via Sirt1-ERK1/2- STAT3 Pathway in Ovarian Cancer Progression.
Liang N, Chen H, Yang Y … +4 more , Guo B, Xu Z, Li L, Jin Y
Curr Gene Ther · 2026 · PMID 41177805 · Publisher ↗
INTRODUCTION: Epithelial Ovarian Cancer (EOC) is a highly aggressive gynecological malignancy with a high mortality rate primarily due to late-stage diagnosis and metastatic dissemination. Regulatory T cells (Tregs) have...
INTRODUCTION: Epithelial Ovarian Cancer (EOC) is a highly aggressive gynecological malignancy with a high mortality rate primarily due to late-stage diagnosis and metastatic dissemination. Regulatory T cells (Tregs) have emerged as critical mediators of immune evasion, yet the role of Foxp3 Tregs in modulating Tumor-Associated Macrophage (TAM) polarization and the underlying molecular mechanisms in EOC remains unclear. METHODS: An orthotopic EOC mouse model and in vitro co-culture systems were employed to investigate the effects of Foxp3 Tregs on TAM polarization. Quantitative Real-Time PCR (qRTPCR), flow cytometry, Western blotting, wound healing, and transwell assays were performed to assess gene expression, immune cell infiltration, and tumor cell migration/invasion. Foxp3 knockdown was achieved using Adeno-Associated Virus (AAV)-mediated delivery to evaluate its effects in vivo. RESULTS: Foxp3 Tregs induced macrophage polarization toward the M2 phenotype, characterized by downregulation of M1 markers (IL-1β, iNOS) and upregulation of M2 markers (IL-10, Arg-1). Mechanistically, Foxp3 Tregs activated the Sirt1-ERK1/2-STAT3 signaling pathway while suppressing NF-κB activity. In vitro, Foxp3 Tregs enhanced the migratory and invasive capacities of ovarian cancer cells, whereas in vivo Foxp3 knockdown significantly reduced tumor growth and M2 macrophage infiltration. DISCUSSION: These findings suggest that Foxp3 Tregs play a pivotal role in shaping the immunosuppressive tumor microenvironment in EOC by promoting M2 macrophage polarization through Sirt1-ERK1/2-STAT3 signaling and NF-κB suppression, ultimately facilitating tumor progression. CONCLUSION: Foxp3 Tregs drive immunosuppressive macrophage polarization and ovarian cancer progression, highlighting Foxp3 as a potential therapeutic target for EOC treatment.
Attenuated Salmonella Carrying IL-21-siRNA-CCR2 Co-expression Plasmid Enhances Anti-tumor Immune Response in Lung Cancer-bearing Mice.
Li J, Li K, Yang J … +11 more , Mo M, Han B, Chen J, Geng J, Lei M, Chen P, Shao M, Jiang H, Zhao T, Jia H, Wang W
Curr Gene Ther · 2025 Oct · PMID 41147281 · Publisher ↗
INTRODUCTION: 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 freq...
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: The combination of IL-21 and CCR2 blockade exerts a synergistic anti-lung-cancer effect.
Preface-2026.
Guan F
Curr Gene Ther · 2026 · PMID 41133837 · Publisher ↗
Abstract loading — click title to view on PubMed.
Revolution of Traditional Chinese Medicine in Anticancer Therapy, Applications and Future Perspective.
Ahuja A, Singh S
Curr Gene Ther · 2025 Oct · PMID 41116275 · Publisher ↗
<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 explor...
<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.
5-Alpha Reductase Deficiency - An Uncommon Disorder of Sexual Development: A Case Study of Four Turkish Patients within a Family.
Ors A, Bereketoglu MB, Boz A … +1 more , Akkus G
Curr Gene Ther · 2026 · PMID 41102955 · Publisher ↗
INTRODUCTION: 5-alpha reductase deficiency is an inherited autosomal recessive disorder that can present with severe masculinization defects and ambiguous genitalia. Up to more than 100 mutations have been reported, but...
INTRODUCTION: 5-alpha reductase deficiency is an inherited autosomal recessive disorder that can present with severe masculinization defects and ambiguous genitalia. Up to more than 100 mutations have been reported, but phenotype and genotype associations have not been directly evidenced. Testosterone-to-dihydrotestosterone (T/DHT) ratio is a clinically diagnostic test, and the cut-off value is expected to be higher than 10. CASE PRESENTATION: This brief report of 4 patients with SRD5A2 deficiency in the same family has focused on the clinical and biochemical features of patients with the same mutation. A 14-year-old patient with c193G>C, p. Ala65Pro in SRD5A2 gene had primary amenorrhea and bilateral palpable mass in the inguinal canal. After a detailed physical examination and karyotype analysis, the patient was diagnosed with SRD5A2 deficiency with a 46, XY karyotype. In addition, the other affected siblings had the same clinical phenotype and low masculinization score. T/DHT ratio of all siblings was 14.5, 2.1, 3.7, and 19.2, respectively. Although all of them had the same genetic mutations with a homozygous pattern (c193G>C, p. Ala65Pro), a different T/DHT ratio was observed in our study. CONCLUSION: The definitive diagnosis of SRD5A2 deficiency requires molecular testing, but it is currently not available in some centers. Therefore, clinical phenotype and biochemical screening, especially the T/DHT ratio, should be used for evaluating this hereditary syndrome. However, we must consider that the diagnostic sensitivity of the stimulated T/DHT ratio can be affected by various factors, such as age, ethnicity, or the presence of residual enzyme activity.
Precision Medicine: Design of Immune Inert Exosomes for Targeted Gene Delivery.
Saad FA
Curr Gene Ther · 2025 Sep · PMID 41031497 · Publisher ↗
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...
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.
A Comprehensive Review of Genetic Risk Factors for Alzheimer's Disease Development.
Kakkar A, Singh H, Anand A … +3 more , Mishra AK, Kumar A, Chopra H
Curr Gene Ther · 2025 Sep · PMID 40990281 · Publisher ↗
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 emerg...
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.
Advancing Antibacterial Strategies: CRISPR-Phage-Mediated Gene Therapy Targeting Bacterial Resistance Genes.
Patel AK, Singh N, Sachan N … +1 more , Chandra P
Curr Gene Ther · 2025 Sep · PMID 40990280 · Publisher ↗
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...
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.
Synergistic Antiproliferative Effects of EGCG and Myricetin on Cervical Cancer Biomarkers in ME180 and SiHa Cell Lines.
Rangaraj K, Vasudevan MT, Rangaraj S … +7 more , Kumar R, Muthusami S, Alahmadi TA, Chinnathambi A, Arulselvan P, Chaiyasut C, Bharathi M
Curr Gene Ther · 2025 Sep · PMID 40976903 · Publisher ↗
INTRODUCTION: Identifying potential biomarkers for the detection, diagnosis, and monitoring of cervical cancer (CC) constitutes a key area for future research. METHODS: Differentially expressed genes (DEGs) and survival-...
INTRODUCTION: Identifying potential biomarkers for the detection, diagnosis, and monitoring of cervical cancer (CC) constitutes a key area for future research. METHODS: 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. RESULTS: 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). DISCUSSION: EGCG and myricetin, in combination, showed a synergistic effect on the ME180 cell line compared to the SiHa cell line. CONCLUSION: More in vitro and cell- and patient-derived xenograft models studies are needed to support the synergistic effect of EGCG and myricetin.
Identifying ARRB2 as a Prognostic Biomarker and Key Player in the Tumor Microenvironment of Pancreatic Cancer through scPagwas Methodology.
Tian G, Liu C, Che C … +11 more , Ren S, Zhang K, Zhou P, Wang K, Lu G, Xia Y, Wang Y, Li K, Yang L, Fan X, Wang L
Curr Gene Ther · 2026 · PMID 40926605 · Publisher ↗
INTRODUCTION: Pancreatic Cancer (PC) is recognized as a highly aggressive malignancy and is anticipated to become the second leading cause of cancer-associated deaths across the United States by 2030. Owing to its late-s...
INTRODUCTION: Pancreatic Cancer (PC) is recognized as a highly aggressive malignancy and is anticipated to become the second leading cause of cancer-associated deaths across the United States by 2030. Owing to its late-stage diagnosis and the substantial risk of metastasis, current therapeutic strategies exhibit limited efficacy, resulting in a five-year survival rate below 10%. Consequently, identifying reliable biomarkers and therapeutic approaches remains imperative for enhancing treatment effectiveness. METHODS: In this study, using the data of Cancer Genome Atlas (TCGA) and Genome-Wide Association Study (GWAS), we identified macrophage subsets and key gene arrb2 closely related to the progression of Pancreatic Adenocarcinoma (PAAD) via the scpagwas method combined with single- cell and bulk transcriptome analysis. RESULTS: The results showed that in macrophage subpopulations closely related to disease progression, the ARRB2 gene was significantly associated with the prognosis of patients, and low expression suggested poor survival outcomes. The high-expression subgroup of ARRB2 exhibited higher sensitivity to a variety of drugs, and i-bet-762 showed strong molecular binding ability with ARRB2. The experimental detection further confirmed the low expression of ARRB2 in PAAD tissue, which provided the basis for its use as a prognostic marker and potential therapeutic target. DISCUSSION: The results of this study suggest that ARRB2 is not only a prognostic biomarker of PAAD but may also be involved in the regulation of metabolic and immune pathways, thereby affecting drug responsiveness. There was a significant difference in drug sensitivity between the high and low-expression subgroups of ARRB2, suggesting that there may be a potential mechanism between the signal pathway and the therapeutic effect, which warrants further functional research. Considering the heterogeneity of the macrophage population and its dual role in tumor promotion and inhibition, in-depth analysis of the context-dependent function of ARRB2 in the immune-rich microenvironment is expected to provide new insights for the development of combination therapy, especially the potential of combining it with BET inhibitors (such as i-bet-762). CONCLUSION: Macrophages, along with ARRB2, serve an essential function in the progression of PAAD and immune regulation. The identification of ARRB2 as a prognostic biomarker and its involvement in critical oncogenic pathways furnish a theoretical foundation for targeted therapeutic interventions. These discoveries contribute to the ongoing exploration of diagnostic, prognostic, and treatment strategies for PAAD.
Unraveling Etiological Indications and Therapeutic Implications of Familial Cerebral Cavernous Malformations in the Dawn of Gene Therapy for Monogenic Conditions.
Ma K, Regmi M, Liu S … +7 more , Xiong Y, Wang Y, Liu W, Dai Y, Lin G, Yang J, Yang C
Curr Gene Ther · 2025 Aug · PMID 40917023 · Publisher ↗
Cerebral Cavernous Malformations (CCMs) are vascular anomalies in the central nervous system that arise from both genetic and non-genetic factors, and can cause hemorrhage, seizures, and neurological deficits. Approximat...
Cerebral Cavernous Malformations (CCMs) are vascular anomalies in the central nervous system that arise from both genetic and non-genetic factors, and can cause hemorrhage, seizures, and neurological deficits. Approximately 80% of CCMs are sporadic, while 20% are Familial (FCCMs), an autosomal dominant, monogenic disorder characterized by multiple lesions and severe clinical manifestations. Over the past three decades, linkage analyses have identified KRIT1/CCM1, MGC4607/CCM2, and PDCD10/CCM3 as major pathogenic genes in FCCMs. However, existing surgical and pharmacological treatments have not adequately prevented disease progression, underscoring the need for more effective strategies. Recent advancements in gene editing tools and delivery systems have transformed gene therapy from a laboratory concept to a clinical reality, offering renewed hope for FCCM patients. Given the multifactorial nature, complexity, and neurological comorbidities of FCCMs, exploring non-surgical gene therapies provides a promising approach for addressing these cerebrovascular lesions. This review summarizes the latest progress in gene editing for FCCMs and examines its therapeutic potential, while acknowledging both the promising benefits and the remaining uncertainties in this evolving field.
Advances in Gene Therapy Clinical Trials for Hemophilia Care.
Rana AJ, Hussain MS, Jakhmola V … +1 more , Gupta G
Curr Gene Ther · 2025 Sep · PMID 40916408 · Publisher ↗
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 (...
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.
Tailored Therapies for Hereditary Diabetes: Unraveling the Genetic Underpinnings of MODY and Neonatal Diabetes.
Dwivedi J, Kaushal S, Wal P … +5 more , Singh DP, Gupta P, Sowjanya P, Abida, Gasmi A
Curr Gene Ther · 2025 Aug · PMID 40910293 · Publisher ↗
INTRODUCTION: Hereditary forms of diabetes, including Maturity-Onset Diabetes of the Young (MODY) and Neonatal Diabetes Mellitus (NDM), are rare monogenic disorders caused by mutations in genes involved in pancreatic dev...
INTRODUCTION: Hereditary forms of diabetes, including Maturity-Onset Diabetes of the Young (MODY) and Neonatal Diabetes Mellitus (NDM), are rare monogenic disorders caused by mutations in genes involved in pancreatic development, beta-cell function, and insulin secretion. Unlike the polygenic nature of type 1 and type 2 diabetes, these forms provide a unique model for precision medicine. METHODS: A comprehensive literature review was conducted to explore the molecular genetics, clinical features, diagnostic advancements, and therapeutic strategies related to MODY and NDM. Particular focus was placed on genotype-phenotype correlations and responsiveness to targeted treatments. RESULTS: Distinct gene mutations such as GCK, HNF1A, and HNF4A in MODY, and KCNJ11, ABCC8, and INS in NDM are associated with specific clinical characteristics and treatment responses. Genetic testing plays a crucial role in early diagnosis and management. For instance, sulfonylurea therapy has effectively replaced insulin in some cases of NDMre with KATP channel mutations. In MODY, accurate genetic classification helps guide the use of oral hypoglycemics or dietary interventions instead of unnecessary insulin therapy. DISCUSSION: Understanding the genetic basis of MODY and NDM has enabled clinicians to personalize treatment plans, improving disease outcomes. Genetic diagnosis not only facilitates better classification but also informs prognosis and guides family screening. Despite these advances, challenges remain in access to testing and awareness among healthcare providers. CONCLUSION: Molecular insights into MODY and NDM have revolutionized their diagnosis and treatment. Gene-based therapeutic approaches enhance glycemic control and quality of life, marking a significant step toward precision medicine in diabetes care. Ongoing research will be key to further optimizing individualized treatment strategies.
Targeted Therapies and Computational Approaches in the Management of Crohn's Disease.
Pandey AK, Mukherjee S
Curr Gene Ther · 2025 Aug · PMID 40910202 · Publisher ↗
Crohn's disease (CD), a chronic inflammatory disorder of the gastrointestinal tract, presents significant challenges in clinical medicine due to its multifactorial etiology and varied therapeutic responses. This review e...
Crohn's disease (CD), a chronic inflammatory disorder of the gastrointestinal tract, presents significant challenges in clinical medicine due to its multifactorial etiology and varied therapeutic responses. This review examines the diverse causes of CD, including genetic predispositions identified through genome-wide association studies (GWAS), which involve scanning the genome for single-nucleotide polymorphisms associated with CD risk, as well as environmental triggers, such as diet and alterations in the microbiome. Biomarkers, such as fecal calprotectin and Creactive protein (CRP), as well as genetic markers like NOD2 mutations, provide critical tools for diagnosis and treatment stratification. Advances in computational methodologies, including multiomics analyses and machine learning, have enhanced our understanding of CD pathophysiology and therapeutic outcomes. Traditional treatments, including immunomodulators and biologics, such as anti-TNF agents, have laid the groundwork for novel cytokine-targeted therapies, such as IL-12/23 inhibitors (e.g., ustekinumab) and integrin inhibitors (e.g., vedolizumab), which aim to improve mucosal healing and reduce relapse rates. However, integrating personalized medicine into clinical practice remains challenging due to the heterogeneity of CD and limitations in biomarker validation. The integration of predictive biomarkers with computational tools enables clinicians to tailor therapy at the individual level, improving remission rates, minimizing adverse effects, and enhancing long-term disease control. These personalized strategies show promise in shifting CD management toward a more effective, patient-specific model of care. This review underscores the potential of personalized therapeutic strategies, leveraging molecular and computational insights, to optimize disease management and improve patient outcomes in CD.
Role of Exosomal miRNAs and Epigenetic Modifications in Diabetic Nephropathy: Insights into Novel Diagnostic and Therapeutic Strategies.
Nagaram S, Sen A, Singh V … +3 more , Raj Ps M, Dwivedi S, Bansal A
Curr Gene Ther · 2025 Aug · PMID 40873225 · Publisher ↗
INTRODUCTION: Diabetic Nephropathy (DN) is a leading cause of chronic kidney disease and end-stage renal failure, highlighting the need for improved diagnostic and therapeutic strategies. This review examines the emergin...
INTRODUCTION: Diabetic Nephropathy (DN) is a leading cause of chronic kidney disease and end-stage renal failure, highlighting the need for improved diagnostic and therapeutic strategies. This review examines the emerging roles of exosomal microRNAs (miRNAs) and epigenetic modifications in disease, with a focus on their diagnostic and therapeutic potential. METHODS: A comprehensive analysis of the current literature was conducted, focusing on exosomal miRNAs-particularly miR-21, miR-192, and miR-29-and their impact on inflammatory pathways, such as IL-6 and NF-κB. The role of epigenetic alterations, including DNA methylation, histone modification, and noncoding RNAs, in DN progression is also discussed. Techniques for miRNA detection and exosome isolation are briefly reviewed. RESULTS: Exosomal miRNAs contribute to DN pathophysiology by promoting oxidative stress, inflammation, and fibrosis. Their stability and noninvasive detectability make them promising early biomarkers. Epigenetic modifications further modulate gene expression relevant to disease progression. DISCUSSION: These molecular changes offer novel targets for early diagnosis and therapeutic intervention in DN. The interplay between miRNAs and epigenetic regulation may provide insights into disease heterogeneity and progression. However, limitations exist regarding the standardization of detection techniques and clinical translation, necessitating further research. CONCLUSION: Exosomal miRNAs and epigenetic markers present valuable tools for advancing the diagnosis and personalized treatment of DN. Enhancing detection techniques and understanding their molecular roles could pave the way for more effective clinical applications.
Transcriptomic Signatures in TP53 Positive and Negative Tumor Samples in NSCLC.
Xie M, Liu B, Chen Z … +2 more , Cao T, Zhang X
Curr Gene Ther · 2025 Aug · PMID 40798960 · Publisher ↗
INTRODUCTION: Lung cancer, specifically non-small cell lung cancer (NSCLC), is a leading cause of cancer-related mortality worldwide. TP53, a crucial tumor suppressor gene, is often mutated in various cancers, including...
INTRODUCTION: Lung cancer, specifically non-small cell lung cancer (NSCLC), is a leading cause of cancer-related mortality worldwide. TP53, a crucial tumor suppressor gene, is often mutated in various cancers, including lung cancer. This study focuses on the differences in transcriptomic profiles between TP53-mutated (TP53+) and TP53-wildtype (TP53-) NSCLC tumor samples, aiming to develop a gene signature that can predict overall survival and immune response, particularly in the context of immunotherapy. It aims to identify differentially expressed genes (DEGs) associated with TP53 status in non-small cell lung cancer and develop a gene signature that can predict overall survival and immune response. METHOD: Gene expression profiles from TP53-positive and TP53-negative NSCLC tumor samples were analyzed. Data were sourced from the GEO database (GSE8569, n = 69) and the TCGA database (n = 1026). Differential expression analysis was conducted to identify DEGs, which were further analyzed using LASSO regression to develop a prognostic gene signature. Quantitative PCR (qPCR) was performed to validate the expression of selected genes. RESULTS: A total of 535 DEGs (168 up-regulated, 367 down-regulated) were identified in TP53+ samples. Further analysis with TCGA data narrowed this down to 29 genes, from which 12 were identified as prognostic features using LASSO analysis. This 12-gene signature effectively stratified patients into low- and high-risk groups for overall survival. Differences in immune cell infiltration and immune pathway activity were significant between these groups, indicating the potential of the gene signature to predict immune response. Among the genes analyzed, BMP2, LPXN, IER3, ANLN, TNNT1, OGT, KRT8, BARX2, PRC1, and SNX30 showed statistically significant differences in qPCR results. DISCUSSION: The 12-gene signature demonstrates robust predictive capability for survival outcomes and immune response patterns in NSCLC patients, suggesting its potential clinical utility in precision oncology. The observed correlation between TP53 mutation status and immune microenvironment alterations provides valuable insights into the mechanistic basis of immunotherapy resistance and response. CONCLUSION: This study identifies a TP53-associated transcriptomic signature that is significantly associated with overall survival in lung cancer patients. The gene signature also correlates with differences in immune cell infiltration patterns between risk groups, offering potential insights into the tumor immune microenvironment. These findings may contribute to future efforts to stratify patients and guide immunotherapy decisions, pending further experimental validation.
A Paradigm Shift in Hemophilia Care: The Promise of Gene Therapy.
Anver Pasha SF, Khalifa Anver TF, Srinivasamurthy SK
Curr Gene Ther · 2026 · PMID 40785174 · Publisher ↗
INTRODUCTION: The discovery of the gene as the primary unit of inheritance marked the beginning of intensive research into targeted genome modifications for treating rare genetic diseases. Despite conventional approaches...
INTRODUCTION: The discovery of the gene as the primary unit of inheritance marked the beginning of intensive research into targeted genome modifications for treating rare genetic diseases. Despite conventional approaches such as continuous factor replacement or novel non-factor therapies, the need for a one-time infusion and long-term sustenance of clotting factors is evident. This review focuses on gene therapies discovered to treat patients with hemophilia. This narrative review seeks to highlight the current potential of gene therapies for hemophilia, elucidate their mode of action, and assess their long-term effectiveness and clinical significance. METHODS: A literature search in PubMed, Embase, Google Scholar, and Scopus databases was done using search terms like gene therapy, viral vectors, Roctavian, hemophilia, etranacogene dezaparvovec, AAV, and FIX-Padua variant. RESULTS: Following intensive clinical trials and successful outcomes, the currently available FDAapproved gene therapies include valoctocogene roxaparvovec (Roctavian) for hemophilia A and etranacogene dezaparvovec (Hemgenix), and fidanacogene elaparvovec (Beqvez) for hemophilia B, and an antibody-based therapy, Marstacimab (Hympavzi) for both hemophilia A and B. DISCUSSION: Decades of clinical research on introducing gene therapy as a potential therapy for hemophilia A and B have paved the way for successful discovery to overcome the long-term burden of factor replacement and other adjunct therapies. Gene therapy has shown persistent success in hemophilia, with clinical trials demonstrating long-term expression of functional clotting factors (Factor VIII or IX). This has reduced bleeding episodes remarkably and the need for regular factor replacement therapy. Yet the drugs need to be studied further to assess long term safety and efficacy following administration. CONCLUSIONS: Gene therapy has shown new possibilities in hemophilia, with many patients achieving near-normal levels of clotting factors and experiencing a significant reduction in bleeding episodes. However, challenges remain, including potential declines in Factor VIII levels over time, immune responses to viral vectors, and high treatment costs. Ongoing research is focused on improving durability, expanding eligibility, and exploring alternative delivery methods.
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