Current Gene Therapy[JOURNAL]
Sun
200 papers
Shaping the Future of Prostate Cancer Care: The Promise and Pitfalls of Gene- and Cell-Based Therapeutics.
Guleria D, Sandhu NK
Curr Gene Ther · 2026 Apr · PMID 42003078 · Publisher ↗
Prostate Cancer (PCa) affects the population worldwide on a large scale in men. This paper presents a comprehensive overview of the evolving therapeutic landscape for PCa and highlights the promise and challenges of gene...
Prostate Cancer (PCa) affects the population worldwide on a large scale in men. This paper presents a comprehensive overview of the evolving therapeutic landscape for PCa and highlights the promise and challenges of gene- and cell-based strategies. There are various limitations to conventional modalities, such as radiotherapy, chemotherapy, and surgery; however, the growing impact of molecular precision, immunotherapies, and innovative gene-editing tools, such as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated (Cas) system, minimizes the limitations of these conventional therapies. Comparisons of the current progress in Oncolytic Virus (OV) based therapies, viral and non-viral gene delivery systems, and cell-based immunotherapies including Chimeric Antigen Receptor (CAR) T cells and Dendritic Cell (DC) therapies demonstrate both their therapeutic potentials and key challenges to their effectiveness that include Tumor Heterogeneity (TH), immune evasion, and the immunosuppressive Tumor Microenvironment (TME). The combination approach integrates the control point blockade, radiosensitizing chemotherapeutics, and biomarker-guided interventions to improve treatment outcomes. It also provides a perspective for analyzing the future roles of Artificial Intelligence (AI), multi-omics integration, and collaborative research networks in shaping standards that are more personalized to enhance care for PCa patients.
Transcription Factor EB Drives Thrombospondin-1 Expression to Dampen Focal-adhesion Signaling and Limit Post-infarction Cardiac Fibrosis.
Liu C, Zhang Q, Zhou D … +3 more , Li B, Cheng J, Lu Y
Curr Gene Ther · 2026 Apr · PMID 41935359 · Publisher ↗
BACKGROUND: Cardiac fibroblasts (CFs) are essential for cardiac morphogenesis and homeostasis. We investigated whether transcription factor EB (TFEB) directly targeted and suppressed the activation of CFs, aiming to eluc...
BACKGROUND: Cardiac fibroblasts (CFs) are essential for cardiac morphogenesis and homeostasis. We investigated whether transcription factor EB (TFEB) directly targeted and suppressed the activation of CFs, aiming to elucidate its underlying pathological mechanism from the perspectives of gene and cell therapy. METHODS: Following myocardial infarction (MI) induction, we performed transcriptome sequencing of CFs isolated from R26-LSL-TFEB+/+; Acta2-cre (n = 3) and R26-LSL-TFEB+/+ (n = 3) mice. Differential gene expression and functional enrichment analyses were conducted using R software. The binding between TFEB and Thrombospondin-1 (Thbs1) was validated by ChIP-qPCR assay. CFs were extracted from adult mice in the R26-LSL-TFEB+/+; Acta2-cre and R26-LSL-TFEB+/+ groups. Protein expressions of integrin, CD47, CD36, Thbs1, p-paxillin, vinculin, P-FAK, and α- SMA were detected by Western blot. Cell migration was assessed by the wound healing and Transwell assays. RESULTS: TFEB modulated the expression of a broad spectrum of RNAs associated with the transformation of CFs. Pathway analysis revealed significant enrichment in pathways related to extracellular matrix (ECM) receptor interaction and focal adhesion (FA). Notably, both mRNA and protein levels of Thbs1 were markedly elevated in TFEB-overexpressing CFs. Integrated computational prediction and chromatin immunoprecipitation assays identified that TFEB directly bound to the promoter region of Thbs1. This binding was associated with downstream modulation of its receptor network and a concomitant reduction in FA complex activation at the protein level. These findings positioned Thbs1 as a key transcriptional target through which TFEB regulated ECM-related signaling and cellular adhesion dynamics in CFs. DISCUSSION: The current findings showed that the modulation of Thbs1 and associated FA signaling was a mechanism through which TFEB overexpression exerted its anti-fibrotic effects on CFs. This highlighted the TFEB-Thbs1 axis as a potential novel target for developing therapeutic strategies to mitigate cardiac fibrosis. CONCLUSIONS: This study suggested that the protective effect of TFEB against MI injury was associated with the Thbs1/FA signaling pathway, providing a novel potential therapeutic target for cardiac fibrosis.
CFTR mRNA-Based Gene Therapy for Cystic Fibrosis: A Mutation-Agnostic Strategy to Restore Ion Transport Function.
Kumar J, Martand MD, Tripathi AK … +4 more , Agarwal P, Kumar H, Shamim S, Ali S
Curr Gene Ther · 2026 Mar · PMID 41931705 · Publisher ↗
Cystic fibrosis is a severe autosomal recessive disorder caused by mutations in the CFTR gene, leading to dysfunctional chloride ion transport across epithelial cells. This results in the accumulation of thick, sticky mu...
Cystic fibrosis is a severe autosomal recessive disorder caused by mutations in the CFTR gene, leading to dysfunctional chloride ion transport across epithelial cells. This results in the accumulation of thick, sticky mucus, primarily affecting the lungs, pancreas, and gastrointestinal tract, leading to chronic respiratory infections and progressive lung damage. Although CFTR modulators have significantly improved outcomes for some patients, their efficacy is limited to specific mutations, leaving many without adequate treatment. CFTR-mRNA-based gene therapy serves as an advantageous therapeutic method for all mutations, independent of the treatment target. Through synthetic CFTR mRNA delivery to epithelial cells using this method, the cells can synthesize the functional CFTR protein required for proper ion transport and mucus hydration. mRNA therapy avoids nuclear entry and genomic integration, reducing the risk of insertional mutagenesis and long-term genetic alterations. Lipid nanoparticles, together with other non-viral delivery carriers, demonstrate significant potential to protect mRNA structures and enhance their ability to enter cells while promoting protein production. Research conducted using animal models has revealed that mRNA therapy leads to the successful restoration of CFTR function, accompanied by improved airway hydration outcomes. Ongoing challenges exist for this therapy, as mRNA encounters instability issues while triggering immune reactions and requires constant dose delivery. Multiple scientific research fields are collaborating on mRNA engineering advancements, along with the development of delivery technologies and combination therapy strategies, to overcome existing obstacles. The study examines current therapeutic approaches while assessing delivery pathways and pharmaceutical advancements, as well as expected research directions regarding CFTR-mRNA therapy, which demonstrates potential to treat all Cystic fibrosis patients through a single, comprehensive treatment.
Decoding Programmed Cell Death Genes: Innovations in Cancer Diagnosis and Treatment.
Kumar A, Kurmi BD
Curr Gene Ther · 2026 Mar · PMID 41918195 · Publisher ↗
Programmed cell death (PCD) profoundly influences cancer initiation, progression, and therapeutic response through interconnected pathways such as apoptosis, autophagy, ferroptosis, necroptosis, and pyroptosis. This pers...
Programmed cell death (PCD) profoundly influences cancer initiation, progression, and therapeutic response through interconnected pathways such as apoptosis, autophagy, ferroptosis, necroptosis, and pyroptosis. This perspective summarizes recent mechanistic insights, highlights pathway crosstalk, and underscores the diagnostic and therapeutic relevance of PCD-associated genes. Advances in biomarker discovery, targeted small molecules, and the immunomodulatory effects of PCD offer promising avenues for precision oncology. Emphasis is placed on ferroptosis as a rising therapeutic vulnerability and on addressing key challenges, including inflammatory toxicity, pathway switching, and biomarker standardization. Harnessing PCD with improved specificity may enable more effective and durable cancer treatments.
Cas9 Delivery: Focused Ultrasound and Nanotechnology Approaches.
Chaudhary V, Singh AP, Sharma H … +3 more , Taumar D, Gujjar A, Rajpoot I
Curr Gene Ther · 2026 Mar · PMID 41863246 · Publisher ↗
INTRODUCTION: CRISPR-Cas9 enables precise genome editing but faces delivery challenges, including poor cellular uptake, off-target effects, and immune activation. Focused ultrasound (FUS) and nanotechnology-based carrier...
INTRODUCTION: CRISPR-Cas9 enables precise genome editing but faces delivery challenges, including poor cellular uptake, off-target effects, and immune activation. Focused ultrasound (FUS) and nanotechnology-based carriers offer synergistic, non-invasive solutions, enhancing delivery efficiency, tissue penetration, and targeting. METHODS: A systematic search (January 2010-March 2025) of PubMed, Web of Science, Scopus, Embase, and Google Scholar databases, preprint servers, and clinical trial registries identified studies employing FUS, nanoparticles (NPs), or combined approaches for CRISPR-Cas9 delivery. Eligible studies reported outcomes on efficiency, specificity, safety, or therapeutic effect in cell lines, animal models, or humans. Data extraction and quality assessment were performed by two independent reviewers. Narrative synthesis and meta-analysis were conducted where appropriate. RESULTS: Forty-eight studies (21 in vitro, 19 in vivo, 8 clinical) met the inclusion criteria. NPmediated delivery achieved ~75% editing efficiency and enhanced stability versus viral or naked methods. FUS increased tissue penetration by threefold and reduced systemic toxicity. Combined FUS-NP systems improved blood-brain barrier penetration and maintained low off-target rates (>80% of studies) with minimal immune responses. DISCUSSION: Hybrid FUS-NP delivery platforms address key barriers in CRISPR-Cas9 therapy, particularly for neurological, oncological, and genetic disorders. Nonetheless, heterogeneity in NP composition, ultrasound settings, and target genes limits direct comparability, and long-term clinical safety remains underexplored. CONCLUSION: FUS-assisted nanotechnology provides a promising non-viral strategy for precise, safe, and targeted CRISPR-Cas9 delivery. Standardization of technical parameters and regulatory frameworks are essential for successful clinical translation.
Challenges in the Stability, Safety, and Efficacy of Antisense Oligonucleotide Therapeutics.
Jamadade MS, Bhushan R, Mahadik SR … +5 more , Karmakar A, Dhanavath N, Kumar L, Murti K, Kumar N
Curr Gene Ther · 2026 Mar · PMID 41863245 · Publisher ↗
Antisense oligonucleotides represent a promising class of therapeutic agents due to their high specificity in modulating gene expression. These short, single-stranded synthetic sequences (typically 13-25 nucleotides) fun...
Antisense oligonucleotides represent a promising class of therapeutic agents due to their high specificity in modulating gene expression. These short, single-stranded synthetic sequences (typically 13-25 nucleotides) function by binding to complementary RNA targets, thereby influencing RNA processing or translation, primarily through RNase H-mediated degradation. Over the past decade, significant advances in chemical modifications and delivery strategies have led to a notable increase in the number of ASO-based therapies that have reached the market. Despite this progress, several challenges persist, including poor stability in biological fluids, limited cellular uptake, and safety concerns related to off-target effects and immunogenicity. This review provides a comprehensive overview of the mechanisms of action of ASOs, their pharmacological applications, current market status, and clinical progress. Special attention is given to evaluating in vitro and in vivo ASO stability using nanotechnology-based delivery approaches to improve pharmacokinetics/ pharmacodynamics and structural modifications to enhance therapeutic potential. Additionally, we discuss the associated adverse effects and propose strategies to mitigate them.
Gene Therapy for Hemophilia: Innovations, Milestones, and Future Prospects.
Kumar D, Gupta V, Tanwar R … +2 more , Jaiswal NK, Gupta S
Curr Gene Ther · 2026 Mar · PMID 41863244 · Publisher ↗
Haemophilia, a genetic bleeding disorder predominantly affecting males, arises from deficiencies or dysfunctions in clotting factors VIII or IX. Conventional treatments, such as frequent intravenous infusions of clotting...
Haemophilia, a genetic bleeding disorder predominantly affecting males, arises from deficiencies or dysfunctions in clotting factors VIII or IX. Conventional treatments, such as frequent intravenous infusions of clotting factor concentrates, pose challenges in terms of cost, accessibility, and patient adherence. Gene therapy offers a transformative solution by correcting genetic mutations, enabling the body to produce clotting factors endogenously. Indian scientists have recently pioneered advances in this field, employing adeno-associated viral vectors for efficient and safe gene delivery. This approach addresses limitations of traditional therapies, including the development of inhibitors and the need for repetitive infusions. With the integration of cutting-edge genome editing technologies, such as CRISPR/Cas9, hemophilia treatment is poised for long-term efficacy and improved quality of life. Despite these promising developments, challenges remain, including affordability, ethical considerations, and equitable access. This paper highlights the latest breakthroughs, clinical advancements, and future directions in gene therapy for hemophilia, emphasizing India's significant contributions to global research. The findings underscore the potential of gene therapy to shift hemophilia management from routine care to curative strategies, redefining therapeutic possibilities for this chronic condition.
Exploring the Epigenetic Mechanisms Underlying Chronic Diseases: A Comprehensive Review.
Aldahish A, Vasudevan R, Qasim SYA … +5 more , Alshahrani MS, Almohsen LK, Alghanoom SM, AlQahtani AA, Alshahrani WK
Curr Gene Ther · 2026 Mar · PMID 41830123 · Publisher ↗
Epigenetics, the study of heritable changes in gene expression without changes to the DNA sequence, has emerged as an important regulator of disease risk and development. Epigenetic alterations, such as DNA methylation,...
Epigenetics, the study of heritable changes in gene expression without changes to the DNA sequence, has emerged as an important regulator of disease risk and development. Epigenetic alterations, such as DNA methylation, histone modifications, and non-coding RNAs, act as molecular bridges between genetic predisposition and environmental factors. Understanding these changes is critical for determining the pathophysiology of chronic illnesses. This article looks at the involvement of epigenetic mechanisms in chronic diseases such as cardiovascular disease, obesity, depression, Alzheimer's disease, and diabetes mellitus. The emphasis is on recent epigenetic discoveries, their implications for disease risk assessment, and the prospect of epigenetic-based therapeutics in precision medicine. Epigenome-Wide Association Studies (EWAS) and next-generation sequencing technologies have revealed disease-specific epigenetic patterns, underlining their potential as biomarkers for early detection and risk stratification. Epigenetic changes affect important molecular pathways that control metabolic regulation, neuroplasticity, inflammatory response, and cellular homeostasis. Epigenetic modification-targeting therapies, such as DNA methylation inhibitors, histone deacetylase inhibitors, and RNA-based treatments, have shown promise in preclinical and early clinical trials. Epigenetic research offers a transformational framework for understanding the intricate interplay of genetic and environmental variables in chronic illness etiology. Epigenetic alterations are reversible, which opens up new possibilities for therapeutic intervention and individualized therapy. Future research should concentrate on improving epigenetic biomarkers, determining causal links in disease progression, and incorporating epigenetic findings into clinical practice. The advancement of epigenetic medicines has the potential to transform disease prevention, treatment, and global health policies.
Molecular Complexities of Dementia: PAISA Mutations and Targeting TAF2N as Therapeutic Avenues.
Panda SP, Kumar S, Singh M … +1 more , Singh V
Curr Gene Ther · 2026 Mar · PMID 41820211 · Publisher ↗
Millions of individuals worldwide are affected by Alzheimer's disease dementia (ADD) and frontotemporal dementia (FTD), with FTD characterized by degeneration of the frontal and temporal lobes leading to cognitive and be...
Millions of individuals worldwide are affected by Alzheimer's disease dementia (ADD) and frontotemporal dementia (FTD), with FTD characterized by degeneration of the frontal and temporal lobes leading to cognitive and behavioral impairments. A subset of Alzheimer's cases exhibits familial inheritance, with the PAISA mutation, a glutamic acid to alanine substitution at codon 280 (E280A) in the PSEN1 gene, being a primary cause of early-onset dementia. PSEN1 encodes a key component of the γ-secretase complex, which cleaves amyloid precursor protein (APP) to generate beta-amyloid (Aβ) peptides. The PAISA mutation disrupts normal Aβ processing, leading to overproduction or accumulation of Aβ, formation of amyloid plaques, and accelerated progression of dementia. Its prevalence is particularly high in Colombian families, giving rise to the term "PAISA mutation." The APOE genotype further modulates the clinical manifestation in PAISA carriers, with APOE2 potentially delaying disease onset, whereas APOE4 is associated with earlier onset. Recent research highlights TAF2N (also known as RBP56, encoded by TAF15) as a promising therapeutic target, as its modulation may regulate AD-associated genes, reduce toxic Aβ isoforms, modulate tau and APP pathways, protect neurons, and enhance synaptic function. Overall, understanding the molecular effects of PAISA mutations and exploring TAF2N-targeted therapies offers novel avenues for addressing early-onset familial AD, providing insights into broader mechanisms of disease pathogenesis.
Exploiting the Warburg Effect: A Potential Ally for Cancer Treatment.
Soni V
Curr Gene Ther · 2026 Mar · PMID 41820210 · Publisher ↗
Mitochondrial dysfunction and the Warburg effect, characterized by aerobic glycolysis, are hallmarks of cancer metabolism, facilitating tumor progression and resistance to therapies. These metabolic shifts allow cancer c...
Mitochondrial dysfunction and the Warburg effect, characterized by aerobic glycolysis, are hallmarks of cancer metabolism, facilitating tumor progression and resistance to therapies. These metabolic shifts allow cancer cells to prioritize glycolysis over oxidative phosphorylation, contributing to rapid proliferation, immune evasion, and metastasis. This review explores the intricate regulation of the Warburg effect by enzymes, transcription factors, and non-coding RNAs. Key players, such as hexokinase, pyruvate kinase M2, and glucose transporters, are discussed as central drivers of glycolysis. This review highlights therapeutic strategies targeting these pathways, including small-molecule inhibitors, combination therapies, and traditional medicines. Advanced diagnostic tools, such as FDG-PET imaging and metabolic profiling, are evaluated for their potential to personalize cancer treatment. The role of synthetic lethality, immunotherapy, and novel drug combinations in addressing metabolic vulnerabilities is also examined. Furthermore, the review underscores the impact of metabolic reprogramming on the tumor microenvironment and its implications for immune modulation. Targeting the Warburg effect presents a promising avenue for overcoming drug resistance and enhancing cancer therapy. This review provides a comprehensive framework for integrating metabolic reprogramming into advanced therapeutic and diagnostic strategies, paving the way for personalized cancer treatment approaches.
Folic Acid-Conjugated Nanocarriers for Targeted Cancer Therapy: Recent Patents and Future Prospects.
Sharma N, Garg Y, Narang RK … +1 more , Singh A
Curr Gene Ther · 2026 Mar · PMID 41820209 · Publisher ↗
As folate receptors are overexpressed on the surface of many tumor cells, folic acidconjugated nanocarriers have emerged as a promising approach for targeted cancer therapy. These nanocarriers enhance therapeutic efficac...
As folate receptors are overexpressed on the surface of many tumor cells, folic acidconjugated nanocarriers have emerged as a promising approach for targeted cancer therapy. These nanocarriers enhance therapeutic efficacy while reducing systemic toxicity and adverse effects by enabling selective drug delivery. The design, synthesis, and application of folic acid-functionalized nanocarriers such as polymeric nanoparticles, liposomes, dendrimers, and micelles have advanced significantly, as evidenced by recent patents. Key objectives of these developments include improving stability, drug loading capacity, controlled release, and receptor-mediated endocytosis. To translate these targeted nanocarriers from bench to bedside, this study examines significant patents submitted over the past ten years, evaluates their clinical potential, and discusses current challenges and potential future directions.
Revolutionizing Drug and Gene Delivery: Cutting-Edge Smart Polymers for Precision Release.
Singh AP, Shamim, Taumar D … +4 more , Sharma H, Gujjar A, Chaudhary V, Rajpoot I
Curr Gene Ther · 2026 Mar · PMID 41820208 · Publisher ↗
Smart polymer-based drug and gene delivery systems are revolutionizing contemporary therapeutics with their increased specificity, efficacy, and safety. Compared to traditional carriers, smart polymers exhibit stimuli-re...
Smart polymer-based drug and gene delivery systems are revolutionizing contemporary therapeutics with their increased specificity, efficacy, and safety. Compared to traditional carriers, smart polymers exhibit stimuli-responsive behavior, enabling controlled and site-specific drug release in response to physiological cues, such as pH, temperature, or enzyme activity. Such dynamic materials allow accurate drug delivery and minimize systemic toxicity, along with providing improved bioavailability. This review delves into some of the latest developments in stimuliresponsive polymers, nanoplatforms with multiple functions, and hybrid polymer systems, highlighting their potential in controlled drug delivery and theragnostics. Challenges, including biocompatibility, stability, and overcoming biological barriers, such as the blood-brain barrier, are also covered. By combining smart polymers with nanotechnology and targeted personalized medicine strategies, the discipline is set to redefine targeted therapy and maximize therapeutic outcomes.
Discovery of Genes Related to Cuproptosis and Mitophagy to Improve Myocardial Infarction Diagnosis and Treatment.
Xue F, Zhang Y, Chang C … +1 more , Chen Q
Curr Gene Ther · 2026 Feb · PMID 41764607 · Publisher ↗
INTRODUCTION: Emerging evidence links cuproptosis and mitophagy to the progression of myocardial infarction (MI). This study explored cuproptosis- and mitophagy-related gene modules in MI, aiming to identify potential bi...
INTRODUCTION: Emerging evidence links cuproptosis and mitophagy to the progression of myocardial infarction (MI). This study explored cuproptosis- and mitophagy-related gene modules in MI, aiming to identify potential biomarkers to improve MI management. METHODS: The GSE66360 dataset, containing 50 control and 49 MI samples, was obtained from GEO. Differentially expressed genes (DEGs) were identified using the "limma" 3.42.2 package, and pathway differences were analyzed via gene set enrichment analysis (GSEA). After clustering gene modules related to cuproptosis and mitophagy using weighted gene co-expression network analysis (WGCNA), core modular genes were selected. LASSO regression and random forest were employed for feature selection. Immune microenvironment profiling was conducted using singlesample GSEA (ssGSEA) and CIBERSORT algorithms. Finally, potential therapeutic targets were identified using DSigDB and molecular docking. RESULTS: We identified the DEGs between MI and control samples. GSEA analysis showed that these genes were associated with the cell cycle, glycolysis, and the inflammatory signaling pathway. The dark green module identified by WGCNA was correlated with both cuproptosis and mitophagy and enriched in oxidative phosphorylation and immune processes. By combining the core modular genes and DEGs, six hub genes were selected using LASSO and random forests. A 3-gene diagnostic model established based on GPCPD1, S100A8, and CD55 achieved an Area under the Curve (AUC) of 0.959. The three genes were upregulated in MI and correlated with immune infiltration. Molecular docking showed Corbadrine and Dicyclomine were potential therapeutic agents targeting CD55. DISCUSSION: This study highlights the broader implications of linking cuproptosis and mitophagy in MI, proposing a novel perspective on mitochondrial dysfunction as a central hub connecting metabolic stress, immune dysregulation, and cell death. The identified core genes-S100A8, CD55, and GPCPD1-not only serve as potential diagnostic markers but may represent functional nodes at the intersection of copper-dependent cell death and mitochondrial quality control. Their strong association with inflammatory cell infiltration suggests that these genes could influence the post-MI immune microenvironment, potentially affecting both injury progression and repair. Moreover, the feasibility of targeting CD55, as indicated by molecular docking, opens new avenues for therapeutic interventions to modulate complement activation and inflammation. While the findings are computationally derived, they generate testable hypotheses about crosstalk between emerging cell death pathways and immune-metabolic pathways in MI, underscoring the need for future experimental studies to validate these interactions and explore their translational potential in cardiovascular disease. CONCLUSION: The core genes (GPCPD1, S100A8, and CD55) identified in this study not only served as potential diagnostic markers but were also functional nodes in copper-dependent cell death, contributing to MI treatment.
Padlock Assay in Transthyretin Amyloidosis: A Feasibility Study.
Di Certo MG, Gabanella F, Passananti C … +17 more , Corbi N, Onori A, Pisani C, Fiore M, de Vincentiis M, Ferraguti G, Francati S, Bottillo I, Lodato V, Riminucci M, Cambieri C, Libonati L, Moret F, Chimenti C, Corsi A, Inghilleri M, Ceccanti M
Curr Gene Ther · 2026 Feb · PMID 41735206 · Publisher ↗
INTRODUCTION: The ability to distinguish between transcripts that differ by a single nucleotide positions our padlock assay as a highly accurate imaging tool for detecting disorders associated with structural variations...
INTRODUCTION: The ability to distinguish between transcripts that differ by a single nucleotide positions our padlock assay as a highly accurate imaging tool for detecting disorders associated with structural variations in the human genome. In this study, we evaluated the effectiveness of the padlock assay in identifying TTR gene variants in a case of transthyretin amyloidosis (ATTR), a rare multisystemic disease. ATTR may result from autosomal dominant mutations in the TTR gene or occur in a wild-type form. METHODS: We applied the padlock assay in combination with rolling circle amplification (RCA) and fluorescence microscopy, using peripheral blood mononuclear cells (PBMCs) as clinical samples. RESULTS: Using the padlock assay, 1) we detected intracellular TTR transcripts in 80% of PBMCs, including a benign variant caused by a single nucleotide substitution in intron 3, 2) we visualized the subcellular localization of both coding and non-coding regions of TTR transcripts, and 3) through dual staining, we simultaneously detected both wild-type and mutated TTR intron 3 in patient- derived cells. Additionally, we found that PBMCs and platelets are immunoreactive to TTR antibodies, suggesting that immunocompetent cells may contribute to the distribution of TTR protein across tissues and organs. DISCUSSION: We demonstrate that the padlock assay can serve as a non-invasive imaging test capable of spatially detecting genomic variants in ATTR. CONCLUSION: These findings suggest that the padlock assay has potential application in evaluating the efficacy of disease-modifying therapies in extra-hepatic cells. Moreover, this study is the first to highlight PBMCs as a valuable source for advancing our understanding of ATTR pathogenesis and for supporting the development of improved therapeutic approaches.
Glioblastoma Organoid Technology: Approach to Target the Complex Tumor Microenvironment with Promising Drug Responsiveness.
Bisht P, Pandey R, Tabish TA … +4 more , Thorat ND, Kumarasamy M, Murti K, Kumar N
Curr Gene Ther · 2026 Jan · PMID 41588969 · Publisher ↗
Glioblastoma remains one of the most lethal brain tumors with limited therapeutic options and a dismal survival rate, largely due to its highly complex Tumor Microenvironment (TME) and frequent drug resistance. In respon...
Glioblastoma remains one of the most lethal brain tumors with limited therapeutic options and a dismal survival rate, largely due to its highly complex Tumor Microenvironment (TME) and frequent drug resistance. In response, three-dimensional (3D) organoid technology has emerged as a powerful tool for modeling glioblastoma, offering a physiologically relevant in vitro system that closely mimics the in vivo architecture, cellular heterogeneity, and drug response of human tumors. Unlike traditional 2D cultures or animal models, glioblastoma organoids enable highthroughput drug screening, personalized therapy testing, and early diagnostic research by preserving key features of the TME. However, despite their immense promise, current organoid models face substantial limitations, including the absence of immune components, functional vasculature, and region-specific neuronal subtypes, thereby restricting their full translational potential, especially for immunotherapy studies. Existing models, such as genetically engineered cerebral organoids (Neo- Cor) and glioblastoma spheroid co-cultures (GLICO), either fail to reflect patient heterogeneity or are constrained by time-intensive preparation. Additionally, patient-derived organoids may lose genetic fidelity over prolonged culture. The novelty of this work lies in its advocacy for engineered cell-based strategies and Adult Stem Cell (AdSC)-derived organoids to overcome these challenges. By enhancing the intrinsic properties of organoid cells and integrating endothelial and immune components, this approach offers a next-generation platform for more accurate modeling of glioblastoma, with greater relevance for drug responsiveness, chemosensitization studies, gene editing, and regenerative applications. This distinguishes the present work from previous studies by not only identifying the gaps in current organoid technologies but also proposing specific, actionable improvements that bring organoid culture closer to clinical translation in glioblastoma research.
Nano-vaccines in Pandemic Preparedness: Pioneering Rapid Development and Deployment for Global Immunity.
Taumar D, Singh AP, Sharma H … +3 more , Gujjar A, Rajpoot I, Chaudhary V
Curr Gene Ther · 2026 Jan · PMID 41588968 · Publisher ↗
BACKGROUND: The increasing frequency of global pandemics, such as COVID-19, H1N1, and Ebola, highlights the urgent need for innovative vaccine technologies that enable rapid response and broader accessibility. Nanovaccin...
BACKGROUND: The increasing frequency of global pandemics, such as COVID-19, H1N1, and Ebola, highlights the urgent need for innovative vaccine technologies that enable rapid response and broader accessibility. Nanovaccines, leveraging nanotechnology for targeted antigen delivery and enhanced immune activation, have emerged as a promising solution for improving vaccine efficacy, stability, and distribution. OBJECTIVE: This review examines the role of nano vaccines in pandemic preparedness, focusing on their benefits, mechanisms of action, recent advancements, and the challenges associated with their development and deployment. METHODS: A comprehensive literature review was conducted using databases such as PubMed, Scopus, and Web of Science. Research articles and clinical trial data from the past decade were analyzed, with a focus on nano-vaccine platforms, immune response mechanisms, and global deployment strategies. KEY FINDINGS: Nanovaccines offer accelerated development timelines, enhanced antigen presentation, and prolonged immune responses via platforms including lipid-based nanoparticles, polymeric systems, virus-like particles, and inorganic nanoparticles. The success of mRNA vaccines during COVID-19 has demonstrated the transformative potential of nanotechnology in vaccine development. However, significant challenges remain, including safety concerns, large-scale manufacturing, regulatory approval procedures, and equitable access, particularly in low- and middle-income countries. CONCLUSION: Nanovaccines offer substantial promise for global pandemic preparedness. Tackling current challenges through international collaboration, policy support, and increased investment will be essential for ensuring their widespread adoption. Developing nanotechnology-driven vaccine solutions can strengthen global health resilience and enable faster, more effective responses to future pandemics.
Advancements in CAR-T Cell Therapy for Ovarian Cancer: Current Strategies and Future Directions.
Liu Y, Ai H
Curr Gene Ther · 2026 Jan · PMID 41588967 · Publisher ↗
Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a transformative approach in oncology, particularly for hematologic malignancies. However, its application to solid tumors, such as ovarian cancer, remains ch...
Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a transformative approach in oncology, particularly for hematologic malignancies. However, its application to solid tumors, such as ovarian cancer, remains challenging. This review discusses recent advancements in CAR-T cell therapy specifically targeting ovarian cancer, with a focus on current strategies and future directions. We first introduce the fundamental structure of CARs, detailing the core components including the antigen-binding domain, the transmembrane domain, and the signaling domains. The optimization of CAR-T design is then examined, highlighting innovative strategies such as bispecific CAR-Ts, co-expression CAR-Ts, fine-tuning of CAR constructs, and cytokine-modified CAR-Ts. The review further explores a comprehensive array of antigen targets relevant to ovarian cancer, ranging from HER2 and mesothelin to more novel targets like CD47 and L1CAM. Additionally, we investigate how nanotechnology is enhancing CAR-T cell therapy for solid tumors, with specific attention to mRNA delivery systems, liposomal nanoparticles, hydrogel-based platforms, and the integration of photothermal therapy.
Identification and Experimental Validation of NOP10 as a Biomarker for Diffuse Large B-Cell Lymphoma.
Zhang T, He L, Zhu Y
Curr Gene Ther · 2026 Jan · PMID 41540529 · Publisher ↗
INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is the most common non- Hodgkin lymphoma. Despite its high prevalence, treatment options remain limited, and molecular mechanisms underlying its pathogenesis remain poo...
INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is the most common non- Hodgkin lymphoma. Despite its high prevalence, treatment options remain limited, and molecular mechanisms underlying its pathogenesis remain poorly understood. This study aimed to identify potential biomarkers for DLBCL by integrating microarray analysis, Mendelian randomization (MR), and experimental validation. MATERIALS AND METHODS: DLBCL-related microarray datasets were downloaded from the Gene Expression Omnibus database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify hub genes in DLBCL. Moreover, we integrated genome-wide association studies data with expression quantitative trait loci to identify genes with potential causal relationships to DLBCL. The predictive power of the identified biomarker gene was evaluated using receiver operating characteristic (ROC) curves. Functional experiments were conducted to elucidate the biological roles of this gene. RESULTS: Differential expression analysis and WGCNA identified 119 differentially expressed genes and 156 central genes, resulting in the identification of 16 hub genes in DLBCL. MR analysis revealed 188 genes with significant causal associations with DLBCL, ultimately identifying nucleolar protein 10 (NOP10) as a key biomarker. NOP10 demonstrated strong predictive performance, with the area under the curve values consistently above 0.852 across all datasets. Experimental validation in DLBCL cell lines showed that NOP10 knockdown significantly inhibited cell proliferation, induced apoptosis, and reduced the migratory capacity. DISCUSSION: Although recent studies have made progress in identifying biomarkers associated with lymphoma onset and progression, establishing causality remains challenging due to reverse causation and confounding factors. The integration of MR in this study addressed these limitations by inferring the causality between exposure and outcome. Our findings were experimentally validated. The combination of microarray analysis and MR in our analytical approach provides a robust framework for identifying biomarker genes in various diseases and guiding the development of future therapeutic strategies. CONCLUSION: Our study has identified NOP10 as a promising biomarker of DLBCL, providing potential insights into the molecular mechanisms underlying this disease. Moreover, a multi-method approach integrating microarray analysis, MR, and experimental validation has established a robust framework for advancing biomarker discovery and identifying therapeutic targets for various diseases.
Targeted TP53 and KRAS Modulation AuNP-Mediated RNA Delivery Suppresses Cancer Progression.
Dündar M, Derin DÇ, Menevşe İN … +2 more , Gültekin E, Koç A
Curr Gene Ther · 2026 Jan · PMID 41540528 · Publisher ↗
BACKGROUND: Small RNAs play a pivotal role in gene regulation, mediating RNAinduced transcriptional activation and post-transcriptional gene silencing. Their high specificity and versatility make them indispensable tools...
BACKGROUND: Small RNAs play a pivotal role in gene regulation, mediating RNAinduced transcriptional activation and post-transcriptional gene silencing. Their high specificity and versatility make them indispensable tools for investigating gene function, elucidating disease mechanisms, and developing targeted therapeutic strategies. METHODS: We developed an AuNP-based RNA delivery system to enhance stability and uptake of therapeutic RNAs targeting TP53 and KRAS pathways. AuNPs were synthesized via citrate reduction and conjugated with siRNA.923 (KRAS-targeting siRNA) and dsP53-285 (p53-stimulating saRNA). A549 and HCT116 cells were transfected with conjugates. Gene expression was analyzed by RT-qPCR and Western blotting. Functional assays, including flow cytometry for cell cycle and apoptosis, MTT and colony formation assays for proliferation, and transwell assays for migration and invasion, were conducted. RESULTS: Individual transfection of AuNP-conjugated siRNA.923 effectively downregulated KRAS expression, whereas AuNP-dsP53-285 upregulated TP53 expression in both A549 and HCT116 cell lines. Co-transfection with AuNP-siRNA.923/dsP53-285 resulted in a significantly greater increase in TP53 mRNA and protein levels, without affecting KRAS mRNA or protein levels, in both cell lines compared with individual transfections. Functionally, the AuNP-based dual small RNA delivery system induced cell cycle arrest at the G0/G1 phase, significantly enhanced apoptosis, and markedly reduced cell proliferation, colony formation, migration, and invasion relative to individual RNA transfections. CONCLUSION: These findings demonstrate that AuNP-mediated co-delivery of siRNA and saRNA effectively modulates the KRAS-p53 signaling axis and enhances therapeutic potential in KRASmutant, TP53-wild-type cancers. Further studies, including in vivo investigations, are warranted to evaluate the translational feasibility and clinical relevance of this combinatorial approach.
CRISPR-Cas9: A Paradigm Shift in Gene Editing Addressing Antimicrobial Resistance.
Devi M, Yashika, Saxena S … +3 more , Niyogi SG, Kishor K, Thakur S
Curr Gene Ther · 2026 Jan · PMID 41508959 · Publisher ↗
The development of traditional antibiotics has stalled due to an escalating antimicrobial resistance (AMR) crisis. Generating new antibiotic development paradigms is critically important. CRISPR-Cas9 gene-editing technol...
The development of traditional antibiotics has stalled due to an escalating antimicrobial resistance (AMR) crisis. Generating new antibiotic development paradigms is critically important. CRISPR-Cas9 gene-editing technology, originally derived from the bacteria's immune system, is now being repurposed to target and neutralize antimicrobial resistance, effectively turning the bacteria's defence mechanisms against them. In this editorial, we outline the opportunities for CRISPRCas9 technology to break the microbial resistance paradigm through specific gene disruption, plasmid targeting, phage therapy, and population-based interventions. We summarize some advances related to CRISPR-Cas9 technology, including a brief overview of the technology, its component technologies, potential applications of genetic targeting, recent research related to the technology, near-future developments, and challenges. As we face an era that has been termed the "postantibiotics" era, CRISPR-Cas9 technology not only represents exciting technology, but also a necessary transitional change for antimicrobial products. This editorial explores recent innovations and data highlighting CRISPR-Cas9's role in addressing AMR, and the scientific, regulatory, and ethical pathways to realizing its full potential in clinical settings.
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