Current gene therapy最新文献

The advent of CRISPR/Cas gene-editing technology has revolutionized molecular biology, offering unprecedented precision and potential in treating genetic disorders, cancers, and other complex diseases. However, for CRISPR/Cas to be truly effective in clinical settings, one of the most significant challenges lies in the delivery of the CRISPR components, including guide RNA (gRNA) and Cas protein, into specific cells or tissues. Safe, targeted, and efficient delivery remains a critical bottleneck. Viral vectors, lipid nanoparticles, and synthetic polymers have been explored, but they come with limitations, such as immunogenicity, toxicity, and limited delivery capacity. Polysaccharide-based delivery systems, with their natural origin, biocompatibility, and versatile chemical properties, offer a promising alternative that could address these delivery challenges while advancing the pharmaceutical applications of CRISPR/Cas gene therapy.

Introduction: Antimicrobial peptides (AMPs), unlike antibiotics, are encoded in genomes. AMPs are exported from the cell after expression and translation. In the case of bacteria, the exported peptides target other microbes to give the producing bacterium a competitive edge. While AMPs are sought after for their similar antimicrobial activity to traditional antibiotics, it is difficult to predict which combinations of amino acids will confer antimicrobial activity. Many computer algorithms have been designed to predict whether a sequence of amino acids will exhibit antimicrobial activity, but the vast majority of validated AMPs in databases are still of eukaryotic origin. This defies common sense since the vast majority of life on Earth is prokaryotic.

Methods: The antimicrobial peptide pipeline, presented here, is a bacteria-centric AMP predictor that predicts AMPs by taking design inspiration from the sequence properties of bacterial genomes with the intention to improve the detection of naturally occurring bacterial AMPs. The pipeline integrates multiple concepts of comparative biology to search for candidate AMPs at the primary, secondary, and tertiary peptide structure levels.

Results: Results showed that the antimicrobial peptide pipeline identifies known AMPs that are missed by state-of-the-art AMP predictors and that the pipeline yields more AMP candidates from real bacterial genomes than from fake genomes, with the rate of AMP detection being significantly higher in the genomes of six nosocomial pathogens than in the fake genomes.

Conclusion: This bacteria-centric AMP pipeline enhances the detection of bacterial AMPs by incorporating sequence properties unique to bacterial genomes. It complements existing tools, addressing gaps in AMP detection and providing a promising avenue for discovering novel antimicrobial peptides.

Background: Individualization of the therapeutic plan for cancer patients is the essence of modern clinical practice. Standard cancer diagnostic and prognostic factors are invasive, and their value for the stratification of cancer patients with a higher risk of local or distant recurrence is limited. YKL-40 is a protumor glycoprotein linked to the immunosuppressive tumor in a microenvironment and an important biomarker of cell activation, proliferation, and migration.

Objective: The objective is to update the review, and molecular and clinical research should investigate novel modalities of targeting this glycoprotein for cancer treatment.

Methodology: Relevant studies published in the English language were identified by searching PubMed, Google Scholar, and MEDLINE from January 2000 to December 2023. Published studies that specifically elicited the role of YKL-40 as a biomarker in different types of tumors were included.

Results: YKL-40 cancer prognostic effect was reported in various cancer types.

Conclusion: Since antibodies against YKL-40 can inhibit tumor angiogenesis and cancer progression, it can be suggested as an attractive candidate for chemical cancer therapy and immunomodulation.

Gene therapy and genome editing have emerged as transformative approaches in the management of a diverse range of genetic and acquired diseases. This evaluation offers a thorough examination of the present state and prospects of these innovative technologies. Gene therapy is a prospective approach to the treatment and prevention of a variety of conditions, including complex cancers and inherited genetic disorders, which entail the introduction, removal, or modification of genetic material within a patient's cells. Genome editing, particularly through techniques such as CRISPR-Cas9, enables targeted corrections of genetic defects and opens new possibilities for personalized medicine by allowing for precise modifications at the DNA level. The review addresses the ethical implications, clinical applications, and significant advancements of these technologies. This article endeavors to underscore the substantial influence of gene therapy and genome editing on contemporary medicine by assessing the most recent research and clinical trials, thereby emphasizing their potential to revolutionize disease treatment and management.

This article provides a detailed look at Parkinson's disease (PD), a neurodegenerative ailment mostly known for movement difficulties such tremor, stiffness, and bradykinesia, which affects approximately 1% of persons over the age of 60. Although the precise cause of PD is still unknown, various factors such as pesticide exposure, genetics, and lifestyle choices like smoking and caffeine consumption are thought to play a role in its development. The presence of Lewy bodies characterizes the disease, the aggregation of alpha-synuclein, the loss of dopaminergic neurons in the substantia nigra, and disruptions in basal ganglia circuitry, resulting in both motor and nonmotor symptoms. This review is structured into several key sections, beginning with an exploration of the pathophysiological mechanisms behind PD, including how genetic mutations can lead to deficits in the Ubiquitin Proteasome System and mitochondrial function, which are linked to familial cases of the disease. Following this, the article explores diagnostic methods, such as the UK Brain Bank Criteria, advanced imaging techniques, olfactory testing, and innovative technologies like machine learning, all of which support early detection and accurate diagnosis of PD. Treatment strategies are also comprehensively reviewed, focusing on traditional pharmacological options like levodopa and dopamine agonists, as well as surgical interventions such as deep brain stimulation. Additionally, the review discusses promising new therapies, including immunotherapy aimed at neuroinflammation and gene therapy for disease modification. The impact of lifestyle changes such as exercise and diet on reducing PD risk and enhancing symptom management are also considered. In conclusion, this review highlights the complex nature of Parkinson's disease and underscores the need for a holistic approach that combines pharmacotherapy, advanced treatments, and lifestyle adjustments. By addressing both symptom management and disease modification, these strategies provide hope for improving quality of life.

Introduction: The absence of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) is a hallmark of triple-negative breast cancer (TNBC), which results in fewer treatment options and inferior clinical outcomes. The major histocompatibility complex family includes CD1B. By exposing T cells to lipid antigens, it alters immunological responses. Although the function of CD1B has been investigated in a number of malignancies, its relevance in TNBC has not been fully investigated.

Method: In this study, immunohistochemistry (IHC) analysis of tissue samples and public databases was carried out to examine the expression of CD1B and its implications for prognosis in TNBC.

Result: Compared to normal tissues, TNBC tissues demonstrated significantly higher levels of CD1B expression. Better overall survival, including survival without distant metastases and survival without recurrence, was found to be associated with higher levels. Additionally, more immune cells, primarily memory B cells and regulatory T cells, entering the TNBC region were found to be associated with greater levels of CD1B. It was found that the immunological microenvironment of TNBC was significantly affected by CD1B. The association between CD1B and immune-related pathways was also identified by examining functional enrichment. Drug sensitivity can be used to identify potential CD1B-targeting therapies. According to these results, CD1B might be a useful prognostic indicator and a possible target for treatment in TNBC.

Conclusion: Nevertheless, additional experimental verification is required to verify the clinical significance of CD1B.

Pancreatic cancer remains one of the most aggressive and lethal malignancies, with a dismal prognosis despite advancements in conventional treatment modalities. Gene therapy has emerged as a promising approach to combat pancreatic cancer by targeting the underlying genetic alterations and harnessing the power of the immune system. This review explores the current landscape of gene therapy strategies for pancreatic cancer, including gene replacement therapy, gene silencing, immunotherapy enhancement, and oncolytic virotherapy. Gene replacement therapy aims to restore the function of tumor suppressor genes, such as TP53, while gene silencing targets oncogenes like KRAS (Kirsten rat sarcoma viral oncogene homolog) to inhibit tumor growth. Immunotherapy enhancement, particularly through chimeric antigen receptor (CAR) T-cell therapy, has shown potential in overcoming the immunosuppressive tumor microenvironment. Oncolytic viruses, engineered to replicate in and destroy cancer cells selectively, have demonstrated efficacy in preclinical models and are being evaluated in clinical trials. Recent advances, including the successful treatment of a patient with advanced pancreatic cancer using neoantigen T-cell receptor gene therapy, highlight the potential of personalized gene therapy approaches. However, challenges such as precise gene delivery, tumor heterogeneity, and ethical considerations must be addressed to realize the potential of gene therapy for pancreatic cancer fully. Ongoing research and clinical trials are expected to facilitate the way for the development of safe and effective gene therapies, offering hope for improved outcomes in pancreatic cancer.

The field of drug discovery has long been challenged by the existence of "undruggable" proteins - targets that have resisted traditional small molecule approaches due to their structural or functional characteristics. This review explores the revolutionary potential of small interfering RNA (siRNA) technology in addressing these elusive targets, marking a paradigm shift in therapeutic development. We discuss the historical development of siRNA technology and its unique mechanism of action, which allows for the silencing of virtually any gene, including those coding for proteins previously deemed undruggable. The review provides a comprehensive analysis of the challenges in targeting undruggable proteins and how siRNA approaches are overcoming these obstacles. We examine several case studies of undruggable targets being successfully addressed by siRNA, including oncogenic proteins like KRAS and c-Myc, transcription factors such as NF-κB and STAT3, and proteins involved in complex protein-protein interactions. The article delves into the latest advances in siRNA design, delivery systems, and targeting strategies, highlighting innovations that enhance specificity and reduce off-target effects. We also discuss the challenges facing siRNA therapeutics, including delivery obstacles, potential immune responses, and regulatory considerations. The review concludes with an exploration of future directions, including combination therapies, personalized medicine approaches, and emerging technologies that complement siRNA strategies. By providing a thorough examination of the advances, challenges, and prospects of using siRNA to target undruggable proteins, this review underscores the transformative potential of this technology in expanding the landscape of therapeutic targets and ushering in a new era of precision medicine.

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.

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.