Current Gene Therapy - Online First

Genomic medicine is revolutionizing genetic disease diagnosis and therapy; has a major impact on clinical practice, particularly in diagnosis and treatment. In addition, next-generation sequencing (NGS) has transformed diagnostics. These advances have made genome profiling cost-effective and fast, helping us find pathogenic variations that cause a variety of genetic illnesses. Given its influence on diagnostic methods, NGS mutation detection accuracy and reliability must be assessed. In therapeutics, genomic medicine has introduced precision methods. CRISPR-Cas9 gene editing, and new RNA-based therapies are being evaluated for the treatment of genetic mutations Pharmacogenomics' capacity to customize medication regimens to genetic profiles, optimizing therapeutic results while minimizing side effects, is also evaluated. Although genetic medicine has transformational promise, its widespread acceptance is difficult. Obtaining widespread acceptance of genetic medicine is difficult because of worries around ethical implications, privacy problems, and the possibility for genetic information to be misused. Ethics and privacy issues surrounding genetic information usage require considerable thought. Genomic data integration into clinical practice requires robust regulatory frameworks. The influence of NGS technology and precision treatments on genetic disease diagnosis and therapy is significant. This review emphasizes the importance of assessing diagnostic tools, comprehending novel therapy modalities, and addressing ethical and regulatory issues to enable responsible and successful clinical integration.

Flavonoids exhibit anti-tumor properties against many human cancer cells, indicating their potential as effective anticancer medicines. Oroxylin A (OrA) is a monoflavonoid molecule that shows significant promise against several types of cancer and possesses a substantial anticancer impact while causing minimal harm to normal tissue. Limited studies have provided a systematic review deciphering the role of oroxylin A in combating breast carcinoma. Hence, we thoroughly analyzed existing research to report various mechanism by which OrA impedes tumor advancement in breast carcinoma, including autophagy, cell cycle arrest, angiogenesis suppression, apoptosis, and glycolysis inhibition. We collected several significant research related to the anticancer potential of oroxylin A and demonstrated anticancerous potential of OrA and its specific mode of action in several human carcinomas. Additionally, we have also incorporated several studies to decipher the structure, bioavailability, and anti-breast cancer potential of Oroxylin A in breast cancer. Overall, this review supports the potential of oroxylin A for developing better anti breast cancer therapeutic approach.

Depression is a complex psychiatric disorder that arises from various underlying biological mechanisms. In this review, the role of microRNAs (miRNAs) in modulating gut microbiota-cytokine communication and their potential to unravel the pathophysiology of depression and develop novel therapeutic strategies are discussed. MiRNAs are small non-coding RNA molecules that have emerged as key regulators in the bidirectional signaling of the gut-brain axis by modulating gene expression and fine-tuning an intricate dialogue between the microbiota, immune system, and central nervous system. Results show how gut microbiota can shape miRNA expression in brain regions involved in mood regulation; conversely, evidence is accumulating, elucidating how miRNA perturbations can shape microbial ecology. Gut bacteria-derived short-chain fatty acids (SCFAs) fuel this nexus by exerting effects on neurogenesis, neurotransmitter synthesis, neuroinflammation, affective behavior alterations, and depressive-like phenotypes. Pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β are also known to be associated with depressive symptoms related to altered expression patterns of specific miRNAs across these disorders. This review exposes the novel potential biomarkers and therapeutic targets/strategies to develop innovative methods in the diagnosis and treatment of depression by exploring bidirectional relations among miRNAs, gut microbiota, and cytokines. The knowledge of these molecular networks and pathways has provided the opportunity for designing new-generation therapeutics such as phytobiotics, probiotics, psychobiotics, diet therapies, and nanomedicine based on miRNAs from a future perspective, which will revolutionize the management of mental disorders.

Gallbladder Cancer (GBC) is a highly concerning malignancy, particularly prevalent in the Asian continent, attributed to irregularities in the bile tract. As of 2022, GLOBOCAN data ranks GBC as the 22^nd most common cause of cancer-related mortality globally and the 6th among gastrointestinal cancers. According to recent World Cancer Research statistics, approximately 122,491 new cases of gallbladder cancer were reported by the end of 2022, ranking it 23^rd among cancers in men and 20^th in women worldwide. Towards the therapy of GBC, genetic studies have provided valuable insights into the molecular mechanisms driving GBC. Mutations in TP53, KRAS, ERBB2 (HER2), CDKN2A, and PIK3CA play crucial roles in tumor initiation and progression. Additionally, epigenetic modifications and aberrant signaling pathways, including Wnt/β-catenin, Notch, and PI3K/AKT/mTOR, have been implicated in GBC pathogenesis. Exploring these genetic alterations has led to targeted therapies, such as HER2 inhibitors (trastuzumab, pertuzumab) and immune checkpoint inhibitors, offering new treatment prospects. Further, current treatment approaches, including surgical resection, chemotherapy (gemcitabine-cisplatin), and radiation therapy, offer suboptimal outcomes in advanced stages of GBC. Despite its prevalence, effective therapeutic approaches and early-stage diagnostic methods remain elusive. This review provides a comprehensive overview of GBC, including its genetic mutations, epidemiology, risk factors, prevention, diagnosis, treatment options, and challenges. This work aims to offer valuable insights into the various factors directly or indirectly associated with GBC, which may assist in preparing an effective strategy against this growing malignancy.

The increasing approval of nucleic acid therapeutics has led to a significant advancement in medicines, demonstrating their potential to revolutionize the prevention and treatment of numerous diseases. However, challenges like nuclease degradation and difficult cellular delivery hinder their use as therapeutic agents. The rising demand for precise gene therapy delivery has positioned nanobiosystems as a groundbreaking solution, with their customizable properties enabling targeted and efficient delivery. Nucleic Acid therapeutics, encompassing antisense DNA, mRNA, small interfering RNA (siRNA), and microRNA (miRNA), have been rigorously investigated for their capacity to modulate gene expression. Notably, integrating these gene therapies with nanoscale delivery platforms has significantly broadened their scope, facilitating sophisticated advancements in bioanalysis, gene silencing, protein replacement therapies, and the development of vaccines. This review provides a thorough review of recent advancements in nanobiosystems for therapeutic nucleic acid delivery. We explore the unique characteristics of various nanobiosystems, including gene therapy-based delivery, nanoparticles, stimuli-responsive systems, smart nanocarriers, and extracellular vesicle-based delivery. We offer a detailed overview of their applications in nucleic acid delivery. Furthermore, we address biological barriers and strategies for the therapeutic delivery of nucleic acids. Ultimately, this review provides critical insights into the strategic development of next-generation delivery vectors for nucleic acid therapeutics.

NGS (Next-generation sequencing) has emerged as the primary approach for gene finding in uncommon hereditary disorders. Targeted gene panels, whole genome sequencing (WGS), and whole exome sequencing (WES) are uses of next-generation sequencing and other related technologies. It is possible to explain personal or individual genome sequencing using NGS technology, as well as to detect disease-causing mutations using NGS findings. NGS, deep sequencing or massively parallel are similar words that describe a method of DNA sequencing leading to revolutionary change in genomic research. Due to its cost-effectiveness, Whole-Exome sequencing (WES) using Next-Generation Sequencing (NGS) is becoming increasingly popular in the field of human genetics. As a diagnostic tool, this technology can reduce the duration of the diagnostic process for several patients and has mostly made a significant contribution to the identification of new genes responsible for causing diseases. Considering the diverse range of phenotypic presentations of the diagnosis, NGS has the potential to uncover causative mutations, including de novo, new, and familial variants, related to epileptic syndromes and significantly enhance molecular diagnosis. The present study centres on the potential applications of next-generation exome sequencing in clinical diagnostics and the challenges encountered in the data processing of such data.

The relentless pursuit of understanding and combating glioblastoma (GBM), one of the most formidable foes in the realm of cancer, requires a deeper exploration of its intricate dynamics. Gliomas, particularly GBM, are known for their lethal nature, and a significant aspect of their pathogenesis lies in their ability to manipulate the blood vessels that sustain them. This complex relationship is governed by a multitude of molecular mechanisms involving a diverse array of cell types within the tumor microenvironment. Central to this intricate web of regulation are non-coding RNAs (ncRNAs), enigmatic molecules that have recently emerged as key players in cancer biology. These ncRNAs wield a remarkable influence on gene expression, often via epigenetic modifications and intricate control over angiogenesis-related molecules. Their role in GBM angiogenesis adds another layer of complexity to our understanding of this disease. In the realm of cancer therapeutics, targeting angiogenesis has become a prominent strategy. However, the efficacy of current anti-angiogenic treatments against GBM is often transient, as these tumors can rapidly develop resistance, becoming even more aggressive. GBM employs a diverse set of strategies to foster its abnormal vasculature, which, in turn, holds the key to understanding why anti-angiogenic therapies often fall short of expectations. This review aims to shed light on potential strategies and novel perspectives to overcome GBM 's resistance to anti-angiogenic therapy. By exploring innovative approaches, including those centered on ncRNAs, we strive to chart a course toward more effective treatments. This journey into the depths of GBM 's complexities offers not only hope but also a blueprint for future research and therapeutic development. As we uncover the intricate mechanisms at play, we inch closer to the day when GBM is no longer an insurmountable adversary in the fight against cancer.