Current Gene Therapy[JOURNAL]
Sun
200 papers
Synergizing CRISPR-Cas9 with Advanced Artificial Intelligence and Machine Learning for Precision Drug Delivery: Technological Nexus and Regulatory Insights.
Roy AA, Pokale R, Mukharya A … +5 more , Nikam AN, Dua K, Rao BSS, Seetharam RN, Mutalik S
Curr Gene Ther · 2025 · PMID 39871553 · Publisher ↗
The evolution of genetic exploration tools, from laborious methods like radiationinduced mutations to the transformative CRISPR-Cas9 system, has fundamentally reshaped genetic research and gene editing capabilities. This...
The evolution of genetic exploration tools, from laborious methods like radiationinduced mutations to the transformative CRISPR-Cas9 system, has fundamentally reshaped genetic research and gene editing capabilities. This journey, initiated by foundational techniques such as ZFNs and TALENs and culminating in the groundbreaking work of Doudna and Charpentier in 2012, has ushered in an era of precise DNA alteration and profound insights into gene functions. The CRISPR/Cas9 system uses the Cas9 enzyme and guides RNA (gRNA) to precisely target and cleave DNA, with subsequent repair via error-prone NHEJ or precise HDR, enabling versatile gene editing. Complementary computational tools like E-CRISP and Azimuth 2.0, alongside advanced deep learning models like DeepCRISPR, have significantly contributed to refining CRISPR experiments, optimizing gRNA efficiency, and predicting outcomes with greater precision. In clinical applications, CRISPR-Cas9 shows great promise for treating complex genetic disorders like sickle cell disease and β-thalassemia, but faces challenges such as off-target effects, immune responses to viral vectors, and ethical issues in germline editing. Overcoming these challenges requires meticulous experimentation and robust regulatory frameworks to ensure responsible and beneficial utilization of the CRISPR-Cas9 technology across diverse fields, including cancer treatment, genetic disease therapies, agriculture, and synthetic biology, while continually addressing ethical, safety, and legal considerations for its advancement and widespread adoption.
Molecular Insights into RNA Modifications and Their Role in Shaping Immune Responses and Tumor Microenvironments.
Ali A, Ajmal T, Khatoon A … +7 more , Akbar K, Irshad U, Murtaza B, Ji Z, Ali A, Tanveer Q, Su Z
Curr Gene Ther · 2025 · PMID 39844555 · Publisher ↗
RNA modifications play crucial roles in immune system development and function, with dynamic changes essential for diverse cellular processes. Innovative profiling technologies are invaluable for understanding the signif...
RNA modifications play crucial roles in immune system development and function, with dynamic changes essential for diverse cellular processes. Innovative profiling technologies are invaluable for understanding the significance of these modifications in immune cells, both in healthy and diseased states. This review explores the utility of such technologies in uncovering the functions of RNA modifications and their impact on immune responses. Additionally, it delves into the mechanisms through which aberrant RNA modifications influence the tumor microenvironments immune milieu. Despite significant progress, several outstanding research questions remain, highlighting the need for further investigation into the molecular mechanisms underlying RNA modification's effects on immune function in various contexts.
Exploring Genetic and Receptor-Based Dopaminergic Strategies for Antidepressant Drug Development.
Pannu A, Goyal RK
Curr Gene Ther · 2025 · PMID 39844554 · Publisher ↗
The dopamine (DA) system is central to mood regulation, motivation, and reward processing, making it a critical focus for understanding Major Depressive Disorder (MDD). While the dopaminergic system's role in MDD pathoph...
The dopamine (DA) system is central to mood regulation, motivation, and reward processing, making it a critical focus for understanding Major Depressive Disorder (MDD). While the dopaminergic system's role in MDD pathophysiology has been acknowledged, gaps remain in linking specific receptor subtypes and genetic factors to depression-like phenotypes. This study explores the interplay between dopamine receptor subtypes (D1-D5) and associated genetic variations, particularly focusing on receptor heterodimers and polymorphisms influencing dopamine biosynthesis, signalling, and metabolism. A comprehensive review of molecular mechanisms highlights key findings; alterations in D1-D2 heterodimers contribute to mood dysregulation; D3 receptor downregulation correlates with depressive behaviour; and genetic polymorphisms, including those in tyrosine hydroxylase and dopamine transporter (DAT) genes, influence dopamine levels and receptor functions. Emerging data from neuroimaging and animal models confirm the pivotal role of dopamine receptor subtypes in MDD, offering insights into their therapeutic targeting. Here, we show that dopaminergic dysfunction underpins MDD's pathophysiology, with receptor-specific mechanisms presenting novel drug targets. Understanding these pathways facilitates precision medicine approaches, bridging the gap between genetic predisposition and receptor pharmacology, and paving the way for tailored antidepressant strategies with improved efficacy and reduced side effects.
Plasmalogens Activate AKT/mTOR Signaling to Attenuate Reactive Oxygen Species Production in Spinal Cord Injury.
Cheng M, Gao Y, Wu Y … +3 more , Zhang L, Xu B, Lu X
Curr Gene Ther · 2025 · PMID 39838674 · Publisher ↗
BACKGROUND: Plasmalogens, the primary phospholipids in the brain, possess intrinsic antioxidant properties and are crucial components of the myelin sheath surrounding neuronal axons. While their neuroprotective effects h...
BACKGROUND: Plasmalogens, the primary phospholipids in the brain, possess intrinsic antioxidant properties and are crucial components of the myelin sheath surrounding neuronal axons. While their neuroprotective effects have been demonstrated in Alzheimer's disease, their potential benefits in spinal cord injury remain unexplored. This study investigates the reparative effects of plasmalogens on spinal cord injury and the underlying mechanisms. METHODS: In vitro, we developed dorsal root ganglion (DRG) and RAW 264.7 cell models under high-reactive oxygen species (ROS) conditions to assess ROS levels, neuronal damage, and inflammatory microenvironment changes before and after plasmalogen application. In vivo, we used a complete mouse spinal cord transection model to evaluate changes in ROS levels, neuronal demyelination, and apoptosis following plasmalogen treatment. Additionally, we assessed sensory and motor function recovery and investigated the regulatory effects of plasmalogens on the AKT/mTOR signaling pathway. RESULTS: In high-ROS cell models, plasmalogens protected DRG neurons (TUJ-1) from axonal damage and modulated the proinflammatory/anti-inflammatory balance in RAW 264.7 cells. In vivo, plasmalogens significantly reduced ROS levels, improved the immune microenvironment, decreased the proinflammatory (iNOS)/anti-inflammatory (ARG-1) ratio, lowered neuronal (TUJ-1) apoptosis (Caspase-3, BAX), and reduced axonal degeneration while promoting myelin (MBP) regeneration, indicating a neuroprotective effect. These findings are linked to the activation of the AKT/mTOR signaling pathway. CONCLUSION: Plasmalogens reduce ROS levels and regulate inflammation-induced damage, contributing to neuroprotection. This study reveals that plasmalogens promote remyelination, reduce axonal degeneration and neuronal apoptosis, and-used here for the first time in spinal cord injury repair- may protect neurons by reducing ROS levels and activating the AKT/mTOR signaling pathway.
siRNA Knocking Down in HepG2 Cells Identifies PFKFB4 and HNF4α as Key Genes Important for Cancer Cell Survival.
Imraish A, Alshaer W, Abu-Thiab T … +5 more , Enaya F, Al-Ameer HJ, Alhunaiti A, Abumurad M, Zihlif M
Curr Gene Ther · 2025 · PMID 39835559 · Publisher ↗
INTRODUCTION: Liposomes are versatile delivery systems for encapsulating small interfering RNAs (siRNAs) because they enhance cellular uptake and gene silencing. This study compares the new liposome formula to commercial...
INTRODUCTION: Liposomes are versatile delivery systems for encapsulating small interfering RNAs (siRNAs) because they enhance cellular uptake and gene silencing. This study compares the new liposome formula to commercial lipofectamine in delivering siRNAs targeting hepatic carcinoma genes, focusing on HNF4-α and PFKFB4. METHODS: Flow cytometry and confocal microscopy revealed efficient internalization of PE-Rhod- B labeled lipoplexes in HepG2 cells, while cytotoxicity assays demonstrated significant reductions in cell viability, particularly with siHNF4-α and siPFKFB4. RESULTS: The newly formulated liposomes showed superior efficacy, achieving nearly 93% cytotoxicity at 100 nM, compared to just 50% with lipofectamine at the same concentration. Furthermore, real-time PCR confirmed that the liposome-encapsulated siHNF4-α reduced HNF4-α mRNA expression by tenfold at 100 nM, compared to a twofold reduction with lipofectamine at 200 nM. Similarly, siPFKFB4 delivered via liposomes showed a dose-dependent 35-fold reduction in PFKFB4 mRNA expression at 100 nM, outperforming the maximum reduction achieved by lipofectamine. The IC values for all siRNA treatment groups were significantly lower when using the liposome formula, reflecting improved delivery efficiency. CONCLUSION: These results demonstrate the potential of liposome formulations for therapeutic siRNA delivery. The encapsulation enhances cellular uptake and gene silencing efficiency, making the liposome formula a promising candidate for targeted gene therapy in hepatic carcinoma. Further research should explore it's in vivo biodistribution and potential combination therapies.
Development of Lentiviral Packaging Cells and Scale Up of Production to Meet the Growing Demand in Cell and Gene Therapy.
van Heuvel Y, Stitz J
Curr Gene Ther · 2025 · PMID 39812051 · Publisher ↗
Gamma-Retroviral (RVVs) and lentiviral vectors (LVVs) represent indispensable tools in somatic gene therapy, mediating the efficient, stable transfer of therapeutic genes into a variety of human target cells. LVVs, in co...
Gamma-Retroviral (RVVs) and lentiviral vectors (LVVs) represent indispensable tools in somatic gene therapy, mediating the efficient, stable transfer of therapeutic genes into a variety of human target cells. LVVs, in contrast to RVVs, are capable of stably genetically modifying non-proliferating target cells, making them the superior instrument in cell and gene therapy. To date, the LVV manufacturing process employs human embryonic kidney cells (HEK293) and derivatives thereof transiently transfected with multiple plasmids encoding the required viral vector components. Alternatively, stable packaging cell lines were developed and engineered to express all vector components in trans. Currently, these cells are mostly cultured in cell stacks, where they grow adherently in 2D layers, limiting the scale-up of vector production. The production of viral vectors using stable suspension cell lines enables larger-scale production and higher yields under controlled conditions. Here, we review the improvements made to enhance vector safety and production yield. Current advancements in the establishment of stable packaging cell lines enabling inducible and constitutive LVV production are summarized and discussed. Manufacturing processes for lentiviral vectors using bioreactors with perfusion systems are required to meet the growing demand in cell and gene therapy and to reduce production and therapy costs.
-substituted Tertiary Amine-chitosans as Promising Nanocarriers for siRNA Delivery.
Martinez Junior AM, de Oliveira Tiera VA, Tiera MJ
Curr Gene Ther · 2025 · PMID 39810537 · Publisher ↗
INTRODUCTION: The clinical translation of chitosan-based formulations for siRNA delivery has been partially limited by their poor stability/solubility at physiological conditions, although they have good biocompatibility...
INTRODUCTION: The clinical translation of chitosan-based formulations for siRNA delivery has been partially limited by their poor stability/solubility at physiological conditions, although they have good biocompatibility and cost-effectiveness. METHODS: In this study, the chitosan was O-substituted with diisopropylethylamine (DIPEA) groups, which improved its solubility at pH 7.4 by increasing the degree of ionization and enhanced the ability of chitosan to load siRNA at very low amine/phosphate (N/P) ratios. The O-DIPEAchitosan/ siRNA nanopolyplexes were self-assembled by complexation and presented positive Zeta potentials (ζ = +8 to +10 mV), spherical-like morphology, 200-300 nm size, low polydispersity index (PDI < 0.2), and were able to protect the siRNA from degradation by RNAse. Also, the resistance to albumin-induced disassembly and aggregation revealed both good structural and colloidal stabilities of the siRNA nanopolyplexes. RESULTS: The nanopolyplexes displayed low cytotoxicities in RAW 264.7 macrophages and were successfully uptaken by both macrophages and HeLa cells achieving internalization efficiency similar to Lipofectamine. A positive correlation was observed between the physicochemical properties of the siRNA nanocarrier and its transfection efficiency. CONCLUSION: A knockdown of about 60-70% of tumor necrosis factor alpha (TNFα) was reached in lipopolysaccharide-stimulated macrophages treated with O-DIPEA-chitosan/siTNFα nanopolyplexes. Overall, the results confirmed that O-DIPEA chitosans are promising carriers for siRNA delivery.
Implications of EBV-Encoded and EBV-Related miRNAs in Tumors.
Awasthi P, Kohli AS, Dwivedi M … +1 more , Hasan S
Curr Gene Ther · 2025 · PMID 39791165 · Publisher ↗
Over 90% of people are infected with the human g-herpesvirus known as the Epstein- Barr virus (EBV). Cancers, such as gastric carcinoma, non-Hodgkin's lymphoma, nasopharyngeal carcinoma, Hodgkin's lymphoma, and Burkitt l...
Over 90% of people are infected with the human g-herpesvirus known as the Epstein- Barr virus (EBV). Cancers, such as gastric carcinoma, non-Hodgkin's lymphoma, nasopharyngeal carcinoma, Hodgkin's lymphoma, and Burkitt lymphoma, are thought to be linked with EBV. It is noteworthy that the first virus discovered that encodes microRNAs (miRNAs) was EBV, and these miRNAs show expression at the different phases of EBV infection. There is growing evidence that EBV-encoded miRNAs influence the growth of EBV-associated tumors. These EBV miRNAs, i.e., BamHI-H rightward fragment 1-derived microRNAs (BHRF1miRNA) and BamHI-A rightward fragment-derived microRNAs (BART miRNAs), are crucial for the persistence of viral infection and the avoidance of host defenses. Currently, significant advancements have been made in analyzing the microRNAs that are found in the duration of EBV infection, in vitro studies identified molecular targets of miRNAs and in vivo studies enhanced our understanding regarding the pathophysiology of these molecules. An extensive look into the pro-carcinogenic impact of microRNAs associated with EBV will increase our understanding of the molecular mechanisms of EBV-associated tumors. In this paper, we have highlighted the functions of miRNAs in EBV infection as well as recent developments in miRNA-based therapeutic and diagnostic approaches that could be useful for EBV-related malignancies. Significantly, targeted therapies against EBV miRNAs are advancing rapidly, with emerging approaches such as miRNA sponges, anti-miRNA oligonucleotides, and CRISPR/Cas9 technologies. These innovations indicate the imminent onset of a new era in the treatment of EBV-associated tumors.
CRISPR/Cas System: A Powerful Strategy to Improve Monogenic Human Diseases as Therapeutic Delivery; Current Applications and Challenges.
Saberi F, Yousefi-Najafabadi Z, Shams F … +14 more , Dehghan Z, Ahmadi S, Pilehchi T, Noori E, Esmaeelzadeh Z, Bazgiri M, Mohammadi R, Khani F, Sameni M, Moradbeigi P, Kardar GA, Salehi M, Teng Y, Jajarmi V
Curr Gene Ther · 2025 · PMID 39781718 · Publisher ↗
The 5,000 to 8,000 monogenic diseases are inherited disorders leading to mutations in a single gene. These diseases usually appear in childhood and sometimes lead to morbidity or premature death. Although treatments for...
The 5,000 to 8,000 monogenic diseases are inherited disorders leading to mutations in a single gene. These diseases usually appear in childhood and sometimes lead to morbidity or premature death. Although treatments for such diseases exist, gene therapy is considered an effective and targeted method and has been used in clinics for monogenic diseases since 1989. Monogenic diseases are good candidates for novel therapeutic technologies like gene editing approaches to repair gene mutations. Clustered regularly interspaced short palindromic repeats (CRISPR)-based systems, the pioneer and effective gene editing tool, are utilized for and treatment of monogenic diseases. The current review provides an overview of recent therapeutic applications of CRISPR-based gene editing in monogenic diseases in and ex vivo models. Furthermore, this review consolidates strategies aimed at providing new treatment options with gene therapy, thereby serving as a valuable reference for advancing the treatment landscape for patients with monogenic disorders.
Untangling the Genetic Threads of Alzheimer's: Insights into Risk Factors and Biomarkers.
Naiyeri A, Moqadami A, Khalaj-Kondori M
Curr Gene Ther · 2025 · PMID 39781717 · Publisher ↗
Dementia is a comprehensive term that refers to illnesses characterized by a decline in cognitive memory and other cognitive functions, affecting a person's overall ability to operate. The exact causes of dementia are un...
Dementia is a comprehensive term that refers to illnesses characterized by a decline in cognitive memory and other cognitive functions, affecting a person's overall ability to operate. The exact causes of dementia are unknown to this day. The heterogeneity of Alzheimer's indicates the contribution of genetic polymorphism to this disease. This disease is the most prevalent and damaging illness. Studies indicate that the global prevalence of Alzheimer's disease (AD) exceeds 26 million individuals. Investigation of variations in many genes indicates that these variations may be linked to the susceptibility to AD. Additional genetic factors could potentially influence AD. Analysis of several single-nucleotide polymorphisms in this context reveals a correlation between certain variants and AD. Regardless, Alzheimer's disease is always influenced by a particular APOE gene allele. The study's findings indicate that risk of Alzheimer's disease (AD) is linked to polymorphisms in the following genes: BDNF, presenilin-1 (PS-1), presenilin-2 (PS-2), LRP, APP, CTSD,5-6HT, TREM2, TNF-α, LPL, Clusterin (CLU), SORL1 (Sortilin-Related Receptor), PICALM, Complement Receptor 1 (CR1), and APOE genes.
The Role of Immunotherapy in Lung Cancer Treatment: Current Strategies, Future Directions, and Insights into Metastasis and Immune Microenvironment.
Li CL, Ma XY, Yi P
Curr Gene Ther · 2025 · PMID 39779552 · Publisher ↗
Lung cancer is a leading cause of mortality worldwide. Immunotherapy has emerged as a potentially effective strategy, as traditional medicines have shown minimal success. This review investigates the current state of imm...
Lung cancer is a leading cause of mortality worldwide. Immunotherapy has emerged as a potentially effective strategy, as traditional medicines have shown minimal success. This review investigates the current state of immunotherapy for lung cancer treatment, focusing on its mechanisms, clinical applications, strategies, and future directions. This study focuses on the different characteristics of non-small and small-cell lung cancer to emphasize the need for targeted treatment strategies. In non-small cell lung cancer, immune checkpoint inhibitors that target PD-1, PDL1, and CTLA-4 have shown a strong therapeutic benefit and increased survival rates. The complex interactions among tumor cells, immune cells, and the tumor microenvironment significantly impact the outcome of immunotherapy. The determination of predicting biomarkers and conquering resistance requires an understanding of the tumor microenvironment. This study addresses a range of immunotherapeutic strategies, such as immune modulators, monoclonal antibodies, and cancer vaccines. The combination approaches are being explored to enhance treatment effectiveness and address resistance mechanisms that integrate immunotherapy with other modalities. Despite advancements, challenges still exist. The identification of reliable biomarkers, regulating immune- related adverse effects, and the overcoming of limitations in treating metastatic disease require more investigation. Future research directions should include exploring the immune microenvironment, developing personalized treatment strategies based on tumor profiles, and integrating new technologies for patient screening. Immunotherapy holds immense potential to modify lung cancer treatment and enhance clinical results.
Identification of the Metabolic Characteristic of Organ Fibrosis Using Microbial Analysis on RNA-seq Data.
Wang Z, Wang P, He G … +4 more , Cheng L, Li T, Wang Y, Li H
Curr Gene Ther · 2025 · PMID 39773047 · Publisher ↗
BACKGROUND: Fibrosis refers to abnormal deposition of extracellular matrix, which leads to organ dysfunction. Metabolic alterations, especially enhanced glycolysis and suppressed fatty acid oxidation, are recognized as a...
BACKGROUND: Fibrosis refers to abnormal deposition of extracellular matrix, which leads to organ dysfunction. Metabolic alterations, especially enhanced glycolysis and suppressed fatty acid oxidation, are recognized as an essential pathogenic process of fibrosis. Recently, several reports indicate that the changes in microbiota composition are associated with metabolic disorders, suggesting microbes may contribute to organ fibrosis by regulating metabolic processes. METHODS: In this study, microbial reannotation was carried out on the RNA-seq data of fibrotic organs. Then, the microbial composition differences among healthy and fibrotic organ samples were determined by alpha and beta diversity analysis. Common and specific microbial markers of fibrosis were also identified by LEfSe. After that, the correlation analysis of the characteristic microbegene- functional pathway was conducted to confirm the effects of microbes on host metabolism. RESULTS: The results showed that the microbial composition significantly differed between healthy and diseased organs. Besides, the common characteristic microbes interacted closely with each other and contributed to fibrosis through symbiosis or inhibition. The largest proportion in fibrosis organs was Proteobacteria, which was the main source of pathogenic microbes. CONCLUSION: Further study found that the metabolic alteration driven by common and special characteristic microbes in fibrotic organs focused on the processes related to glycolysis and fatty acid metabolism.
From DNA Editing to RNA Regulation: The Breakthroughs of CRISPR and Mega-CRISPR.
Kumar D, Sil D, Komal … +2 more , Kurmi BD, Kumar M
Curr Gene Ther · 2025 · PMID 39633520 · Publisher ↗
Abstract loading — click title to view on PubMed.
Unraveling Glioblastoma: TME Implication and Gene Therapy Advances.
Raali R, Suresh PK
Curr Gene Ther · 2025 · PMID 39543872 · Publisher ↗
Glioblastoma is a malignant manifestation of a solid brain tumour with a very dismal prognosis due to an overall median survival of 14 months. The currently administered Standard treatment plan, the STUPP regimen, is not...
Glioblastoma is a malignant manifestation of a solid brain tumour with a very dismal prognosis due to an overall median survival of 14 months. The currently administered Standard treatment plan, the STUPP regimen, is not very effective in tackling this neoplasia. A major concern that affects the development of new drug formulations, specifically for Glioma, is the inherent sub-clonal heterogeneity, which includes the dynamic and intricate nature of the Tumour Microenvironment (TME). Targeting the cellular niche using personalized medication for glioma specifically gene therapy, seems to be promising, with most studies in preclinical models yielding optimistic results. This paper analyses the great headways made in glioma gene therapy in the last 10 years while looking into different therapeutic strategies. That said, certain challenges do plague the clinical use of gene therapy which have been highlighted in the hopes that future researchers will address these concerns and further propel gene therapy in its journey from the Lab to the bedside.
Comprehensive Analysis and Experimental Validation of HEPACAM2 as a Potential Prognosis Biomarker and Immunotherapy Target in Colorectal Cancer.
Wang S, Zhang L, Li D … +1 more , Gou M
Curr Gene Ther · 2025 · PMID 39492767 · Publisher ↗
BACKGROUND: The role of HEPACAM family member 2 (HEPACAM2) is unclear in colorectal cancer (CRC). OBJECTIVE: The objective of this study was to perform an extensive examination of HEPACAM2 and validate it experimentally...
BACKGROUND: The role of HEPACAM family member 2 (HEPACAM2) is unclear in colorectal cancer (CRC). OBJECTIVE: The objective of this study was to perform an extensive examination of HEPACAM2 and validate it experimentally in CRC. METHODS: This study investigated the significance of HEPACAM2 in CRC and its potential diagnostic utility utilizing data from the Cancer Genome Atlas (TCGA) database. Additionally, the study examined potential regulatory networks involving HEPACAM2, including its associations with immune infiltration, immune checkpoint genes, tumor mutational burden (TMB), microsatellite instability (MSI), mRNA expression-based stemness index (mRNAsi), and drug sensitivity in CRC. The expression of HEPACAM2 was further validated using the GSE89076 dataset, and quantitative reverse transcription PCR (qRT-PCR) was employed to confirm HEPACAM2 expression levels in six pairs of CRC tissue samples. RESULTS: HEPACAM2 exhibited abnormal expression patterns in various types of cancer, including CRC. A decrease in HEPACAM2 expression levels in CRC was found to be significantly correlated with the T stage (p < 0.001). Reduced HEPACAM2 expression in CRC patients was also linked to poorer overall survival (OS) (p = 0.007). The expression levels of HEPACAM2 in CRC patients were identified as an independent prognostic factor (p = 0.016). Furthermore, HEPACAM2 was associated with TCF-dependent signaling in response to WNT, G2/M checkpoints, and other pathways. The expression of HEPACAM2 in CRC was found to be associated with immune infiltration, immune checkpoint genes, TMB / MSI, and mRNAsi. Additionally, the expression of HEPACAM2 in CRC was significantly and inversely correlated with the drug sensitivities to gw772405x and 6-phenyl-6h-indeno[1,2-c]isoquinoline-5,11-dione. qRT-PCR confirmed that the expression level of HEPACAM2 was found to be lowly expressed in CRC tissues. CONCLUSION: These findings suggest that HEPACAM2 may serve as a potential prognostic biomarker and immunotherapeutic target for CRC patients.
Probing the Depths of Molecular Complexity: STAT3 as a Key Architect in Colorectal Cancer Pathogenesis.
Suleman M, Khan SU, Ali S … +4 more , Alghamdi A, Alissa M, Mushtaq RY, Crovella S
Curr Gene Ther · 2025 · PMID 39473261 · Publisher ↗
Colorectal cancer (CRC) has become a significant threat in recent decades, and its incidence is predicted to continue rising. Despite notable advancements in therapeutic strategies, managing CRC poses complex challenges,...
Colorectal cancer (CRC) has become a significant threat in recent decades, and its incidence is predicted to continue rising. Despite notable advancements in therapeutic strategies, managing CRC poses complex challenges, primarily due to the lack of clinically feasible therapeutic targets. Among the myriad molecules implicated in CRC, the signal transducer and activator of transcription 3 (STAT3) stands out as a promising target tightly regulated by various genes. This intracellular transcription factor, spanning 750-795 amino acids and weighing approximately 92 kDa, is crucial in key cellular activities such as growth, migration, invasion, inflammation, and angiogenesis. Aberrant activation of STAT3 signaling has been linked to various cancers, including CRC. Therefore, targeting this signaling pathway holds significance for potential CRC treatment strategies. STAT3, as a central intracellular transcription factor, is implicated in colorectal cancer development by activating aberrant signaling pathways. Numerous studies have demonstrated that the abnormal hyperactivation of STAT3 in CRC tissues enhances cell proliferation, suppresses apoptosis, promotes angiogenesis, and facilitates tumor invasion and metastasis. As a focal point in colorectal cancer research, STAT3 emerges as a promising candidate for detecting and treating CRC. This review aims to present recent data on STAT3, emphasizing the activation and functions of STAT3 inhibitors in CRC. Indeed, STAT3 inhibitors have been identified to have therapeutic potential in CRC, especially inhibitors targeting the DNA-binding domain (DBD). Indeed, STAT3 inhibitors have been identified to have a therapeutic potential in CRC, especially the inhibitors targeting the DNA binding domain (DBD). For example, imatinib acts by targeting cell surface receptors, and these inhibitors have shown potential for the control and treatment of tumor growth, angiogenesis, and metastasis. Imatinib, for example acts by targeting cell surface receptors, and these inhibitors have shown the future direction toward the control and treatment of tumor growth, angiogenesis, and metastasis.
Efficacy and Safety of Pembrolizumab Monotherapy or Combined Therapy in Patients with Metastatic Triple-negative Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Araghi M, Gharebakhshi F, Faramarzi F … +4 more , Mafi A, Mousavi T, Alimohammadi M, Soleimantabar H
Curr Gene Ther · 2025 · PMID 39468438 · Publisher ↗
BACKGROUND: Metastatic Triple-negative Breast Cancer (mTNBC) is the most aggressive form of breast cancer, with a greater risk of metastasis and recurrence. Research studies have published in-depth analyses of the advant...
BACKGROUND: Metastatic Triple-negative Breast Cancer (mTNBC) is the most aggressive form of breast cancer, with a greater risk of metastasis and recurrence. Research studies have published in-depth analyses of the advantages and disadvantages of pembrolizumab, and early data from numerous trials suggests that patients with mTNBC have had remarkable outcomes. This meta-analysis compares the data from numerous relevant studies in order to evaluate the safety and efficacy of pembrolizumab monotherapy or combination therapies for mTNBC. METHODS: To identify eligible RCTs, a thorough literature search was carried out using electronic databases. CMA software was utilized to perform heterogeneity tests using fixed and random-effects models. RESULTS: According to our pooled data, the median Progression-free Survival (PFS) was 2.66 months, and the median overall survival (OS) was 12.26 months. Furthermore, by comparing efficacy indicators between PD-L1-positive and PD-L1-negative groups, a correlation was found between the overexpression of PD-L1 with OS, PFS, and ORR. Patients with PD-L1-positive tumors had a higher response rate, with an ORR of 21.1%, compared to the patients with PD-L1-negative tumors. The ORR for first-line immunotherapy was higher than that of ≥second-line immunotherapy. In addition, pembrolizumab plus combination treatment resulted in a pooled incidence of immune- related adverse events of 22.7%. CONCLUSION: A modest response to pembrolizumab monotherapy was detected in the mTNBC patients. Furthermore, a better outcome from pembrolizumab treatment may be predicted by PD-L1-- positive status, non-liver/lung metastases, combination therapy, and first-line immunotherapy. Pembrolizumab, in combination with chemotherapy, may be more beneficial for patients whose tumors are PD-L1 positive.
Deep Innovation and Application Exploration of Artificial Intelligence in the Medical Field.
Cheng L
Curr Gene Ther · 2025 · PMID 39468437 · Publisher ↗
Abstract loading — click title to view on PubMed.
Gene Augmentation Techniques to Stimulate Wound Healing Process: Progress and Prospects.
Dwivedi J, Kaushal S, Jeslin D … +4 more , Karpagavalli L, Kumar R, Dev D, Wal P
Curr Gene Ther · 2025 · PMID 39444185 · Publisher ↗
Gene therapy has traditionally been used to treat individuals with late-stage cancers or congenital abnormalities. Numerous prospects for therapeutic genetic modifications have emerged with the discovery that gene therap...
Gene therapy has traditionally been used to treat individuals with late-stage cancers or congenital abnormalities. Numerous prospects for therapeutic genetic modifications have emerged with the discovery that gene therapy applications are far more extensive, particularly in skin and exterior wounds. Cutaneous wound healing is a complex, multistep process involving multiple steps and mediators that operate in a network of activation and inhibition processes. This setting presents a unique obstacle for gene delivery. Many gene delivery strategies have been developed, including liposomal administration, high-pressure injection, viral transfection, and the application of bare DNA. Among several gene transfer techniques, categorical polymers, nanoparticles, and liposomalbased constructs show great promise for non-viral gene transfer in wounds. Clinical experiments have shown that efficient transportation of certain polypeptides to the intended wound location is a crucial factor in wound healing. Genetically engineered cells can be used to produce and control the delivery of specific growth factors, thereby addressing the drawbacks of mechanically administered recombinant growth factors. We have discussed how repair mechanisms are based on molecules and cells, as well as their breakdown, and provided an overview of the methods and research conducted on gene transmission in tissue regeneration.
Immune Modulation Strategies in Gene Therapy: Overcoming Immune Barriers and Enhancing Efficacy.
Amsaveni S, Radha M, Chandrasekaran V … +5 more , Chanchal DK, Mathew S, Sharma MC, Shiekmydeen J, Ali SS
Curr Gene Ther · 2025 · PMID 39360529 · Publisher ↗
The immune system presents significant obstacles to gene therapy, which has limited its use in treating many illnesses. New approaches are needed to overcome these problems and improve the effectiveness of gene therapy....
The immune system presents significant obstacles to gene therapy, which has limited its use in treating many illnesses. New approaches are needed to overcome these problems and improve the effectiveness of gene therapy. This study explores several techniques to immune regulation within gene therapy, a cutting-edge discipline that aims to optimise results by fine-tuning the immune response. We cover new ways to control the immune system and deliver therapeutic genes just where they are needed, including influencing immunological checkpoints, causing immunotolerance, and making smart use of immunomodulatory drugs. In addition, the study provides insight into new developments in the design of less immunogenic gene delivery vectors, which allow for the extension of transgene expression with minimal adverse immune reactions. In order to maximise the efficacy of gene-based therapies, this review analyses these novel approaches and gives a thorough overview of the present state of the art by addressing obstacles and pointing the way toward future developments in immune regulation. Not only does their integration provide new opportunities for the creation of safer and more effective gene treatments, but it also contains the key to overcome current obstacles.
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