CURRENT GENE THERAPY

Comprehensive Analysis and Experimental Validation of HEPACAM2 as a Potential Prognosis Biomarker and Immunotherapy Target in Colorectal Cancer
Wang S, Zhang L, Li D and Gou M
The role of HEPACAM family member 2 (HEPACAM2) is unclear in colorectal cancer (CRC).
Unraveling Glioblastoma: TME Implication and Gene Therapy Advances
Raali R and P K S
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.
Immune Modulation Strategies in Gene Therapy: Overcoming Immune Barriers and Enhancing Efficacy
Amsaveni SS, Mahendran R, C S V, Chanchal DK, Mathew S, Sharma MC, S J and Ali SS
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.
Probing the Depths of Molecular Complexity: STAT3 as a Key Architect in Colorectal Cancer Pathogenesis
Suleman M, Khan SU, Ali S, Alghamdi A, Alissa M, Mushtaq RY and Crovella S
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.
Gene Augmentation Techniques to Stimulate Wound Healing Process: Progress and Prospects
Dwivedi J, Kaushal S, Jeslin D, Karpagavalli L, Kumar R, Dev D and Wal P
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.
Characteristics of Oxidative Phosphorylation-Related Subtypes and Construction of a Prognostic Signature in Ovarian Cancer
Lu J, Zhen S and Li X
Ovarian cancer is associated with a high mortality rate. Oxidative Phosphorylation (OXPHOS) is an active metabolic pathway in cancer; nevertheless, its role in ovarian cancer continues to be ambiguous. Therefore, the objective of this study was to identify the prognostic value of OXPHOS-related genes and the immune landscape in ovarian cancer.
Delivery of Superoxide Dismutase 3 Gene with Baculoviruses Inhibits TNF-α Triggers Vascular Smooth Muscle Cell Proliferation and Inflammation
Lin SL, Lee ST, Huang SE, Chang TH, Geng YJ, Sulistyowati E and Yeh JL
Superoxide dismutase 3 (SOD3), recognized as a potent free radical scavenger, exhibits antioxidant, anti-inflammatory, and anti-angiogenic properties. However, the molecular mechanisms underlying the protective effects of SOD3 on the vascular smooth muscle cell during atherosclerosis remain unclear.
Recent Advances in Therapeutics and Manufacturing Processes of Recombinant Adeno-Associated Virus for the Treatment of Lung Diseases
Sorroza-Martinez L, Pelletier M, Guay D and Gaillet B
Developing delivery vectors capable of transducing genetic material across the lung epithelia and mucus barrier is a major challenge and of great interest to enable gene therapies to treat pulmonary diseases. Recombinant Adeno-associated Viruses (rAAVs) have emerged as attractive candidates among viral and non-viral vectors due to their broad tissue tropism, ability to transduce dividing and quiescent cells, and their safety profile in current human applications. While rAAVs have demonstrated safety in earlier clinical trials for lung disease applications, there are still some limitations regarding rAAV-transgene delivery in pulmonary cells. Thus, further improvements in rAAV engineering are needed to enhance the effectiveness of rAAV-based therapies for lung diseases. Such therapies could benefit patients with chronic lung diseases, such as asthma, chronic obstructive pulmonary disease, pulmonary hypertension, and cystic fibrosis, among others, by regulating hereditary gene mutations or acquired gene deregulations causing these conditions. Alongside therapeutic development, advances in the rAAV production process are essential to meet increasing production demands, while reducing manufacturing costs. This review discusses current challenges and recent advances in the field of rAAV engineering and manufacturing to encourage the clinical development of new pulmonary gene therapy treatments.
DeepLCRmiRNA: A Hybrid Neural Network Approach for Identifying Lung Cancer-Associated miRNAs
Cheng N, Chen C, Liu J, Wang X, Gao Z, Mao M and Huang J
Lung cancer stands as one of the most prevalent malignant neoplasms, with microRNAs (miRNAs) playing a pivotal role in the modulation of gene expression, impacting cancer cell proliferation, invasion, metastasis, immune escape, and resistance to therapy.
Proteogenomic Identification and Analysis of KIF5B as a Prognostic Signature for Hepatocellular Carcinoma
Qi L, Tan Y, Zhou Y, Dong Y, Yang X, Chang S, Yu L and Liu D
Metabolic disorders are significant risk factors for liver cancer, particularly Hepatocellular Carcinoma (HCC). However, the molecular genetic basis of metabolic reprogramming in the liver remains largely uncertain.
Target and Gene-Based Therapeutic Strategies against Pancreatic Cancer: Current and Future Prospects
Dwivedi M, Sanyal S, Singh S, Dwivedi M and Sanyal S
Despite tremendous advancements in knowledge, diagnosis, and availability of both traditional and innovative treatments, pancreatic cancer remains a dangerous disease with a high death rate and dismal prognosis. The traditional strategy in adjuvant and palliative settings is still cytotoxic chemotherapy predicated on the purine derivative gemcitabine; nevertheless, there is an increasing need for new medicines that target the primary molecular pathways and pathophysiological abnormalities implicated. There is now just a tiny amount of evidence of therapeutic benefit when the targeted drug erlotinib is added to the conventional gemcitabine treatment. In preclinical and clinical trials, novel medications targeting mTOR, NF-κB, and proteasome, including the enzyme histone deacetylase, are currently being studied alongside the well-established monoclonal antibody treatments and small-molecule protein tyrosine kinase inhibitors. These novel medications may change the negative natural progression of this illness in conjunction with gene therapy and immunotherapy, both of which are undergoing clinical study. In this regard, leveraging miRNA manipulation to combat cancer is appealing due to its promise to deliver personalized treatment tailored to an individual's distinct gene or miRNA expression profile. Preclinical studies involving animals have showcased the effectiveness of miRNA-based therapies, with several of these treatments now progressing into human clinical trials for various malignancies and other medical conditions. This review describes the important developments of targeted therapeutics that are associated with pancreatic cancer and the discoveries which can help in dealing with this fatal malignancy in a more significant manner.
Pan-Cancer Single-Cell Analysis Revealing the Heterogeneity of Cancer-Associated Fibroblasts in Skin Tumors
Zhang Y, Zhao Z, Huang W, Kim BS, Lin L, Li X, Hou M, Li L, Zhang Y, Xi W and Chai G
Cancer-Associated Fibroblasts (CAFs) constitute a heterogeneous group of cells critical for the remodeling of the tumor microenvironment (TME). Given their significant impact on tumor progression, particularly in skin cancers, a deeper understanding of their characteristics and functions is essential.
Identification of Gene Signatures Associated with COVID-19 across Children, Adolescents, and Adults in the Nasopharynx and Peripheral Blood by Using a Machine Learning Approach
Bao Y, Ren J, Chen L, Guo W, Feng K, Huang T and Cai YD
Significant variations in immune profiles across different age groups manifest distinct clinical symptoms and prognoses in Coronavirus Disease 2019 (COVID-19) patients. Predominantly, severe COVID-19 cases that require hospitalization occur in the elderly, with the risk of severe illness escalating with age among young adults, children, and adolescents.
Hereditary Patterns and Genetic Associations in Obsessive-Compulsive Disorder (OCD): Neuropsychiatric Insights, Genetic Influences, and Treatment Perspectives
Dhiman A, Mehan S, Khan Z, Tiwari A, Gupta GD and Narula AS
Obsessive-Compulsive Disorder (OCD), a prevalent neuropsychiatric condition, affects approximately 2%-3% of the global population. This paper provides an extensive overview of OCD, detailing its clinical manifestations, neurobiological underpinnings, and therapeutic approaches. It examines OCD's classification shift in the DSM-5, the role of the cortico-striatothalamo- cortical pathway in its development, and the various factors contributing to its etiology, such as genes, environmental factors, and genetic predispositions. The challenges in diagnosing OCD and the effectiveness of both psychological and pharmacotherapeutic treatments are discussed. The paper also highlights the significant overlap between OCD and other mental health disorders, emphasizing its impact on global disability. Moreover, the role of genetic factors in OCD, including twin studies and gene association studies, is elaborated, underscoring the complex interplay of hereditary and environmental influences in its manifestation. The review further delves into the polygenic nature of OCD, illustrating how multiple genes contribute to its development, and explores the implications of genetic studies in understanding the disorder's complexity. Additionally, this research study delves into the concept of polygenic inheritance in complex diseases, highlighting the role of multiple genes in increasing OCD risk. A Genome-wide Association Study (GWAS) is employed to assess Single Nucleotide Polymorphisms (SNPs) to unearth genetic associations with OCD. This comprehensive analysis provides valuable insights into OCD's genetic landscape, paving the way for enhanced diagnostic approaches and treatment modalities.
Alternative Splicing of Pre-mRNA Matters in Oral Diseases
Yue M and Jia R
Alternative splicing (AS) of pre-mRNA occurs widely in human genes to produce multiple isoforms with different or even opposite functions. Aberrant AS is often associated with gene mutations and can be corrected by gene therapy. Oral diseases are important public health problems worldwide. Accumulated pieces of evidence demonstrate that AS of pathogenic genes plays key roles in some oral diseases. However, considering the extensiveness and complexity of AS, it may affect the initiation and development of oral diseases deeply and widely. This review describes the diversity of AS and resulting isoforms in genetic, infectious, and malignant oral diseases and highlights the key roles of AS in determining the function of isoforms and the occurrence and progression of these diseases. The studies of alternative splicing may provide great opportunities for the understanding and treatment of oral diseases.
miRNA-Targeted Vaccines: A Promising Approach for Viral Attenuation and Immunogenicity Enhancement
Debnath A, Mazumder R, Mazumder A, Tripathi S, Dua A, Singh R, Mangal S, Sanchitra J, Pandey P, Pal B, Chaudhary H, Sharma P and Srivastava S
MicroRNAs (miRNAs) have emerged as a significant tool in the realm of vaccinology, offering novel approaches to vaccine development. This study investigates the potential of miRNAs in the development of advanced vaccines, with an emphasis on how they regulate immune response and control viral replication. We go over the molecular features of miRNAs, such as their capacity to direct post-transcriptional regulation toward mRNAs, hence regulating the expression of genes in diverse tissues and cells. This property is harnessed to develop live attenuated vaccines that are tissue-specific, enhancing safety and immunogenicity. The review highlights recent advancements in using miRNA-targeted vaccines against viruses like influenza, poliovirus, and tick-borne encephalitis virus, demonstrating their attenuated replication in specific tissues while retaining immunogenicity. We also explored the function of miRNAs in the biology of cancer, highlighting their potential to develop cancer vaccines through targeting miRNAs that are overexpressed in tumor cells. The difficulties in developing miRNA vaccines are also covered in this work, including delivery, stability, off-target effects, and the requirement for individualized cancer treatment plans. We wrap off by discussing the potential of miRNA vaccines and highlighting how they will influence the development of vaccination techniques for cancer and infectious diseases in the future.
The Functions and Application Prospects of Hepatocyte Growth Factor in Reproduction
Mi X, Chen C, Feng C, Qin Y, Chen ZJ, Yang Y and Zhao S
Hepatocyte growth factor (HGF) is expressed in multiple systems and mediates a variety of biological activities, such as mitosis, motility, and morphogenesis. A growing number of studies have revealed the expression patterns and functions of HGF in ovarian and testicular physiology from the prenatal to the adult stage. HGF regulates folliculogenesis and steroidogenesis by modulating the functions of theca cells and granulosa cells in the ovary. It also mediates somatic cell proliferation and steroidogenesis, thereby affecting spermatogenesis in males. In addition to its physiological effects on the reproductive system, HGF has shown advantages in preclinical studies over recent years for the treatment of male and female infertility, particularly in women with premature ovarian insufficiency. This review aims to summarize the pleiotropic functions of HGF in the reproductive system and to provide prospects for its clinical application.
Biogenesis and Function of circRNAs in Pulmonary Fibrosis
Zhang S, Hu W, Lv C and Song X
Pulmonary fibrosis is a class of fibrosing interstitial lung diseases caused by many pathogenic factors inside and outside the lung, with unknown mechanisms and without effective treatment. Therefore, a comprehensive understanding of the molecular mechanism implicated in pulmonary fibrosis pathogenesis is urgently needed to develop new and effective measures. Although circRNAs have been widely acknowledged as new contributors to the occurrence and development of diseases, only a small number of circRNAs have been functionally characterized in pulmonary fibrosis. Here, we systematically review the biogenesis and functions of circRNAs and focus on how circRNAs participate in pulmonary fibrogenesis by influencing various cell fates. Meanwhile, we analyze the current exploration of circRNAs as a diagnostic biomarker, vaccine, and therapeutic target in pulmonary fibrosis and objectively discuss the challenges of circRNA- based therapy for pulmonary fibrosis. We hope that the review of the implication of circRNAs will provide new insights into the development circRNA-based approaches to treat pulmonary fibrosis.
Effect of Bovine Lactoferrin Treatment on Iron Homeostasis and Gene Expression Changes in Multiple Organ Dysfunctions During Wound Healing Process in Rats
Bozkurt AS and Yılmaz ŞG
Injury systemically disrupts the homeostatic balance and can cause organ failure. LF mediates both iron-dependent and iron-independent mechanisms, and the role of LF in regulating iron homeostasis is vital in terms of metabolism.
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, Mafi A, Mousavi T, Alimohammadi M and Soleimantabar H
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.
Deep Innovation and Application Exploration of Artificial Intelligence in the Medical Field
Cheng L