Current Gene Therapy - Volume 23, Issue 4, 2023

Leukemia is a type of cancer that affects white blood cells. In this disease, immature blood cells undergo genetic mutations, leading to excessive replication and reduced cell death compared to healthy cells. In cancer, there may be the activation of oncogenes and the deactivation of tumor suppressor genes that control certain cellular functions. Despite the undeniable contribution to the patient's recovery, conventional cancer treatments may have some not-so-beneficial effects. In this case, gene therapy appears as an alternative to classical treatments. Gene therapy delivers genetic material to cells to replace or modify dysfunctional genes, a safe method for neoplasms. One of the types of nucleic acids explored in gene therapy is microRNA (miRNA), a group of endogenous, non-proteincoding, small single-stranded RNA molecules involved in the regulation of gene expression, cell division, differentiation, angiogenesis, migration, apoptosis, and carcinogenesis. This review aims to bring together the most recent advances found in the literature on cancer gene therapy based on microRNAs in the oncological context, focusing on leukemia.

Currently, an increasing prevalence has been reported in incidences of tumor pathologies. The influence of anesthetics drugs has been the subject of numerous studies. It has been reported that the use of certain drugs may have an impact on prognosis and survival. By investigating the action of these drugs on different metabolic pathways and their mechanisms of action, we can better understand how they influence various hallmarks of carcinogenesis and determine their potential impact on cancer progression. Some of the action pathways are widely known within oncology, being targets of specific treatments, such as PI3k/AKT/mTOR, EGFR, and Wnt/β-catenin. This review performs a thorough dissection of the interaction between anesthetic drugs and oncological cell lines through cell signaling pathways and genetic, immune, and transcriptomic pathways. Through these underlying mechanisms, it aims to clarify the effect of the choice of anesthetic drug and its potential influence on the prognosis of oncological surgery.

Approximately 2% to 3% of men and 6% to 7% of women suffer from severe depressive disorders. The existing drugs only partially relieve symptoms for roughly 40% of these patients. The majority of antidepressant drugs are based on theories that are now 50 to 60 years old, and the sector is in critical need of new drug development targets. In the recent decade, numerous genes have been connected to depression in animal models, and serious depression does run in families in humans, indicating both a genetic and environmental component. Depression has been linked to the malfunctioning of serotonin signaling genes, including p11, SERT, etc, according to earlier research. Gene therapy for depression has been found in some instances to be relatively safe, despite the fact that it may seem riskier and more invasive than medication. Hence, there is a growing field regarding the safest delivery mechanisms of these genes that treat major depressive disorders permanently. Hence, the present review summarized the delivery mechanisms of various genes responsible for depressive disorders along with their molecular mechanisms and delivery at the cellular level.

tsRNAs are small noncoding RNAs that originate from tRNA cleavage and play important regulatory roles in gene expression, translation, transcription, and epigenetic modification. The dysregulation of tsRNAs in cancer disrupts gene expression and perturbs various cellular activities, including cell proliferation, apoptosis, migration, and invasion. Moreover, tsRNAs may influence cancer development by regulating related cell signaling pathways. In this review, we first examine the origins and classification of tsRNAs and their effects on tumor cell activity. To highlight the latest research progress of tsRNAs and signaling pathways, we summarize the possible mechanisms of tsRNAs in specific tumor-related signaling pathways, including the Wnt, TGFb1, MAPK, PI3K-AKT, Notch, and MDM2/p53 signaling pathways, that have been identified in recent research.

Aim: Duchenne Muscular Dystrophy (DMD) results in a deficiency of dystrophin expression in patient muscle fibers, leading to progressive muscle degeneration. Treatment of DMD has undertaken current transformation with the advancement of novel gene therapy and molecular biology techniques, which are secure, well-tolerated, and effective therapeutic approaches. Introduction: DMD gene therapies have mainly focused on young DMD patients as in vivo animal model trials have been performed in 0–1-month DMD mice. However, it has not yet been answered how micro-dystrophin encoding lentiviral treatment affects Dystrophin expression and DMD symptoms in 10-month mdx mice. Methods: We planned to integrate the micro-Dystrophin gene sequence into the muscle cells by viral transfer, using micro-Dystrophin-encoding lentivirus to reduce the dystrophic pathology in late-stage dmd mice. The histopathological and physiological-functional regeneration activities of the lentiviralmicro- Dystrophin gene therapy methods were compared, along with changes in temporal Dystrophin expression and their functionality, toxicity, and gene expression level. Results: Here, we showed that the micro-dystrophin transgene transfers intramuscularly and intraperitoneally in late-stage dmd-mdx-4cv mice restored dystrophin expression in the skeletal and cardiac muscle (p <0.001). Furthermore, motor performance analysis, including hanging and tracking tests, improved statistically significantly after the treatment (p <0.05). Conclusion: Consequently, this study suggests that patients in the late stages of muscular dystrophy can benefit from lentiviral micro-dystrophin gene therapies to present an improvement in dystrophic muscle pathology.

Introduction: The importance of microRNAs (miRNAs) has been emphasized by an increasing number of studies, and it is well-known that miRNA dysregulation is associated with a variety of complex diseases. Revealing the associations between miRNAs and diseases are essential to disease prevention, diagnosis, and treatment. Methods: However, traditional experimental methods in validating the roles of miRNAs in diseases could be very expensive, labor-intensive and time-consuming. Thus, there is a growing interest in predicting miRNA-disease associations by computational methods. Though many computational methods are in this category, their prediction accuracy needs further improvement for downstream experimental validation. In this study, we proposed a novel model to predict miRNA-disease associations by low-rank matrix completion (MDAlmc) integrating miRNA functional similarity, disease semantic similarity, and known miRNA-disease associations. In the 5-fold cross-validation, MDAlmc achieved an average AUROC of 0.8709 and AUPRC of 0.4172, better than those of previous models. Results: Among the case studies of three important human diseases, the top 50 predicted miRNAs of 96% (breast tumors), 98% (lung tumors), and 90% (ovarian tumors) have been confirmed by previous literatures. And the unconfirmed miRNAs were also validated to be potential disease-associated miRNAs. Conclusion: MDAlmc is a valuable computational resource for miRNA–disease association prediction.