Progress in molecular biology and translational science最新文献

β-thalassemia is an autosomal recessive disease, caused by one or more mutations in the β-globin gene that reduces or abolishes β-globin chain synthesis causing an imbalance in the ratio of α- and β-globin chain. Therefore, the ability to target mutations will provide a good result in the treatment of β-thalassemia. RNA therapeutics represents a promising class of drugs inclusive antisense oligonucleotides (ASO), small interfering RNA (siRNA), microRNA (miRNA) and APTAMER have investigated in clinical trials for treatment of human diseases as β-thalassemia; Especially, ASO therapeutics can completely treat β-thalassemia patients by the way of making ASO infiltrating through erythrocyte progenitor cells, migrating to the nucleus and hybridizing with abnormal splicing sites to suppress an abnormal splicing pattern of β-globin pre-mRNA. As a result, the exactly splicing process is restored to increase the expression of β-globin which increases the amount of mature hemoglobin of red blood cells of β-thalassemia patients. Furthermore, current study demonstrates that RNA-based therapeutics get lots of good results for β-thalassemia patients. Then, this chapter focuses on current advances of RNA-based therapeutics and addresses current challenges with their development and application for treatment of β-thalassemia patients.

Cell and gene therapy are innovative biomedical strategies aimed at addressing diseases at their genetic origins. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) systems have become a groundbreaking tool in cell and gene therapy, offering unprecedented precision and versatility in genome editing. This chapter explores the role of CRISPR in gene editing, tracing its historical development and discussing biomolecular formats such as plasmid, RNA, and protein-based approaches. Next, we discuss CRISPR delivery methods, including viral and non-viral vectors, followed by examining the various engineered CRISPR variants for their potential in gene therapy. Finally, we outline emerging clinical applications, highlighting the advancements in CRISPR for breakthrough medical treatments.

Glioblastoma (GBM) is a highly proliferative, lethal cancer of the brain. The median survival at eight months is ca. 6.8%. Resistance towards the anti-glioblastoma drug temozolomide (TMZ), recurrence of cancer cells, blood-tumor brain barrier (BTBB), blood-brain barrier (BBB), and tumor immunosuppression are major challenges in treating GBM. Drug delivery systems employing TMZ and other anti-cancer drugs and combination therapy (temozolomide with immunotherapeutics) are under pre-clinical and clinical studies, respectively. Immunotherapeutics have emerged as a dominant mechanism to silence tumor development and dissemination. Paradoxically, immunotherapy has witnessed failure in treating GBM. This is due to the unique immunosuppressive microenvironment in GBM. Future immunotherapeutics with inherent tumor environment-modulating properties have to be identified. In this review, we discuss recent delivery systems and devices engineered to deliver immunotherapeutics with the ability to alter/silence tumor immune suppression.

Liposomal drug delivery systems stand as versatile therapeutic platforms for precisely targeting related elements in cancerous tissues owing to their intrinsic passive and acquired active targeting capabilities and exceptional compatibility with physiologic environments. When the capacity of liposomes as nanocarriers is combined with the revolutionary potential of RNA therapies in affecting undruggable targets, the outcome would be promising drug candidates as game-changers in the cancer treatment arena. However, optimizing liposome composition, physicochemical properties, and surface chemistry is paramount to maximizing their pharmacokinetic and pharmacodynamic attributes. This review highlighted the potential of liposomes as nanovehicles for RNA therapeutics through a literature review and looked at the most recent preclinical and clinical advancements in utilizing liposomal RNA therapeutics for cancer management. Notably, the discovery of novel targets, advancements in liposome engineering, and organizing well-planned clinical trials would help uncover the incredible potential of these nanotherapeutics in cancer patients.

Atherosclerosis represents a pathological state that affects the arterial system of the organism. This chronic, progressive condition is typified by the accumulation of atheroma within arterial walls. Modulation of RNA molecules through RNA-based therapies has expanded the range of therapeutic options available for neurodegenerative diseases, infectious diseases, cancer, and, more recently, cardiovascular disease (CVD). Presently, microRNAs and small interfering RNAs (siRNAs) are the most widely employed therapeutic strategies for targeting RNA molecules, and for regulating gene expression and protein production. Nevertheless, for these agents to be developed into effective medications, various obstacles must be overcome, including inadequate binding affinity, instability, challenges of delivering to the tissues, immunogenicity, and off-target toxicity. In this comprehensive review, we discuss in detail the current state of RNA interference (RNAi)-based therapies.

RNA therapy involves utilizing RNA-based molecules to control biological pathways, aiming to cure specific diseases. As our understanding of RNA functions and their roles has expanded, the application of RNA therapies has broadened to target various therapeutic points. This approach holds promise for treating a range of diseases, including kidney diseases. Therapeutic RNA can be employed to target specific genes or pathways implicated in the development of kidney conditions, such as inflammation, fibrosis, and oxidative stress. This review highlights the therapeutic potential of RNA-based therapies across different types of kidney diseases, encompassing infection, inflammation, nephrotoxicity, and ischemia/reperfusion injury. Furthermore, studies have pinpointed the specific kidney cells involved in RNA therapy. To address challenges hindering the potential impact of RNA-based drugs on their targets, nanotechnology is integrated, and RNA-loaded vehicles with ligands are explored for more efficient outcomes.

Genome editing involves altering of the DNA in organisms including bacteria, plants, and animals using molecular scissors that helps in treatment and diagnosis of various diseases. Genome editing technology is exponentially growing and have been developed for enabling precise genomic alterations and the addition, removal, and correction of genes. These modifications begin with the creation of double-stranded breaks (DSBs) that is generated by nucleases and can be joined through homology-directed repair (HDR) or non-homologous end-joining (NHEJ). NHEJ is quick but increases mutation chances due to deletions and insertions of nucleotides at the break site, while HDR uses homologous templates for precise repair and targeted DNA specific to the gene or sequence. Other methods such as zinc-finger protein is a transcription factor that binds with DNA and binds specific to that sequence, which uniquely recognise 3-base pairs of DNA. TALENs consists of two domains: TALE domain, a transcription activator and FokI that is a restriction endonuclease that cuts the DNA at specific sites. CRISPR-Cas systems are clustered regularly interspersed short palindromic repeats present in various bacterial species. These sequences activate RNA-guided DNA cleavage, aiding in the development of an adaptive immune defence against foreign DNA. CRISPR-Cas9 is widely used for genome editing, regulation, diagnostic and many.

Cancer has been a primary contributor to morbidity and mortality worldwide. With an increasing trend of incidence and prevalence of cancer, progress has also been made in its treatment, starting from radiation and chemotherapy to immunotherapy and gene therapy. CRISPR-Cas technique, a promising gene editing tool, has been employed in cancer research for novel treatment regimens, identification of therapeutic targets, and unraveling the genetic mechanisms behind oncogenesis. CRISPR-based genome editing helped in identifying the roles of specific genetic factors linked to treatment resistance, metastasis, and cancer development. CRISPR allows the discovery of genes and treatment options through specifically interrupting tumor activators or activating tumor suppressor genes in cancer cells. Advancements in CRISPR technology, especially the use of immune cells like chimeric antigen receptor (CAR) T cells, has the potential to revolutionize personalized cancer treatment by precisely targeting and killing cancer cells. Furthermore, reactivating tumor suppressor genes makes cancer cells more susceptible to chemotherapy or immunotherapy. CRISPR-mediated genome editing can, hence, help to overcome resistance to traditional cancer treatments. The current manuscript covers that how is the CRISPR technology propelling revolutionary development in the field of cancer research, providing advance perspectives on the molecular causes of the disease and creating new lines for the development of more precise and potent cancer therapies.

Despite the extensive advancements made in the field of cancer therapy, the outlook of individuals suffering from glioblastoma multiforme remains highly detrimental. The absence of specific treatments for cancerous cells significantly hinders the effectiveness of conventional anticancer techniques. Multiple research studies have demonstrated that the suppression of specific genes or the augmentation of therapeutic proteins through RNA-based therapeutics may represent a valuable approach when combined with chemotherapy or immunotherapy. In recent years, there has been a significant increase in the application of RNA therapeutics in conjunction with chemotherapy and immunotherapy. This emerging field has become a prominent area of research for advancing various types of cancer treatments. The present investigation provides an in-depth overview of the classification and application of RNA therapy, focusing on the mechanisms of RNA antitumor treatment and the current status of clinical studies on RNA drugs.

Cardiovascular diseases (CVDs) are characterized by abnormalities in the heart, blood vessels, and blood flow. CVDs comprise a diverse set of health issues. There are several types of CVDs like stroke, endothelial dysfunction, thrombosis, atherosclerosis, plaque instability and heart failure. Identification of a new drug for heart disease takes longer duration and its safety efficacy test takes even longer duration of research and approval. This chapter explores drug repurposing, nano-therapy, and plant-based treatments for managing CVDs from existing drugs which saves time and safety issues with testing new drugs. Existing drugs like statins, ACE inhibitor, warfarin, beta blockers, aspirin and metformin have been found to be useful in treating cardiac disease. For better drug delivery, nano therapy is opening new avenues for cardiac research by targeting interleukin (IL), TNF and other proteins by proteome interactome analysis. Nanoparticles enable precise delivery to atherosclerotic plaques, inflammation areas, and damaged cardiac tissues. Advancements in nano therapeutic agents, such as drug-eluting stents and drug-loaded nanoparticles are transforming CVDs management. Plant-based treatments, containing phytochemicals from Botanical sources, have potential cardiovascular benefits. These phytochemicals can mitigate risk factors associated with CVDs. The integration of these strategies opens new avenues for personalized, effective, and minimally invasive cardiovascular care. Altogether, traditional drugs, phytochemicals along with nanoparticles can revolutionize the future cardiac health care by identifying their signaling pathway, mechanism and interactome analysis.