Current Gene Therapy - Online First

MicroRNAs, commonly referred to as miRNAs, exert a significant impact on cellular processes by coordinating post-transcriptional gene regulation. These non-coding RNAs, which are only 22 nucleotides long, form a part of the RNA-induced silencing complex (RISC) and play a crucial role in regulating gene expression. Their complex participation in cell proliferation, differentiation, and death highlights their crucial role in maintaining cellular balance. MicroRNAs have become significant contributors in the complex field of cancer biology, operating beyond the usual tasks of cells. Their dysregulation is closely intertwined with cancer initiation and development. miRNAs act as cellular regulators and regulate complex processes of gene expression. Disruption of this regulation can result in tumor development. This review article explores the intricate process of miRNA biosynthesis and its mechanisms, providing insights into its complex interactions with cancer. It also discusses the exciting field of miRNA-based cancer treatment. Exploring the therapeutic possibilities of these small RNA molecules presents opportunities for precision medicine, introducing a new age where miRNAs can be utilized to create targeted therapeutic interventions that mainly address the abnormal genetic characteristics that cause tumor formation. miRNAs provide a harmonious balance between understanding their biology and utilizing their therapeutic potential in cancer treatment. However, they also serve as conductors and possible therapeutic instruments in the symphony of molecular biology for gene therapy.

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.

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 non-motor 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.

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.