One of the well-known X-linked genetic disorders is hemophilia, which could be hemophilia A as a result of a mutation in the F8 (factor VIII) gene or hemophilia B as a result of a mutation in the F9 (factor IX) gene, leading to insufficient levels of the proteins essential for blood coagulation cascade. In patients with severe hemophilia, factor VIII or factor IX activities in the blood plasma are considerably low, estimated to be less than 1%. This is responsible for spontaneous or post-traumatic bleeding episodes, or both, leading to disease complications and death. Current treatment of hemophilia relies on the prevention of bleeding, which consists of expensive lifelong replacement infusion therapy of blood plasma clotting factors, their recombinant versions, or therapy with recombinant monoclonal antibodies. Recently emerged gene therapy approaches may be a potential game changer that could reshape the therapeutic outcomes of hemophilia A or B using a one-off vector in vivo delivery and aim to achieve long-term endogenous expression of factor VIII or IX. This review examines both traditional approaches to the treatment of hemophilia and modern methods, primarily focusing on gene therapy, to update knowledge in this area. Recent technological advances and gene therapeutics in the pipeline are critically reviewed and summarized. We consider gene therapy to be the most promising method as it may overcome the problems associated with more traditional treatments, such as the need for constant and expensive infusions and the presence of an immune response to the antibody drugs used to treat hemophilia.

Background/Objectives: Since their approval in early 2020, mRNA vaccines have gained significant attention since the COVID-19 pandemic as a potential therapeutic approach to tackle several infectious diseases. This article aims to review the current state of mRNA vaccine technology and its use against other diseases. Methods: To obtain accurate and reliable data, we carefully searched the clinicaltrial.gov and individual companies’ websites for current ongoing clinical trials reports. Also, we accessed different NCBI databases for recent articles or reports of clinical trials, innovative design of mRNA vaccines, and reviews. Results: Significant progress has been made in the design and improvement of mRNA vaccine technology. Currently, there are hundreds of ongoing clinical trials on mRNA vaccines against different cancer types, infectious diseases, and genetic and rare diseases, which showcase the advancement in this technology and their potential therapeutic advantages over traditional vaccine platforms. Finally, we predict what could be a potential future direction in designing more effective mRNA vaccines, particularly against cancer. Conclusions: The results of many of the ongoing clinical trials have shown significant positive outcomes, with many of the trials already at Phase III. Despite this outlook, however, some have been terminated or withdrawn for several reasons, some of which are not made available. This means that despite the advancement, there is a need for more research and critical evaluation of each innovation to better understand their immunological benefits and long-term effects.

Background/Objectives: Since their approval in early 2020, mRNA vaccine has gained significant attention since COVID-19 pandemic as a potential therapeutic approach to tackle several infectious diseases. The aim of this article is to review the current state of mRNA vaccine technology and its use against other diseases. Methods: To get accurate and reliable data, we carefully search the clinicaltrial.gov, and individual company’s website for current ongoing clinical trials reports. Also, we accessed different NCBI databases for recent articles or reports of clinical trials, innovative design of mRNA vaccine and reviews. Results: Significant progress have been made in the design and improvement of mRNA vaccine technology. Currently, there are hundreds of ongoing clinical trials on mRNA vaccine against different cancer types, infectious diseases, and genetic and rare diseases which showcase the advancement in this technology and their potential therapeutic advantages over traditional vaccine platforms. Finally, we project what could be potential future direction in designing more effective mRNA vaccine, particularly against cancer. Conclusions: Results of many of the ongoing clinical trials have shown significant positive outcomes with many of the trials already at phase III. Despite this outlook however, some have been terminated or withdrawn for several reasons, some of which are not made available. This means that despite the advancement, there is need for more research and critical evaluation of each innovation to better understand their immunological benefits and long-term effects.

Rare genetic disorders of the central nervous system (CNS) remain some of the most complex and challenging diseases to treat for several reasons. Targeting the CNS, especially the brain, presents one of the greatest obstacles in gene therapy using adeno-associated virus (AAV) vectors. Although various AAVs have been identified for their ability to transduce different cells in the CNS, their effectiveness and efficiency are significantly limited by the presence of neutralising antibodies (NAbs) and restricted cargo capacity. Despite these challenges, our understanding of AAV structure and technological advances continue to enable researchers to develop innovative strategies that have resulted in groundbreaking, FDA-approved therapeutic products now available for Leber congenital amaurosis (LCA) (Luxturna^®), spinal muscular atrophy (SMA) (Zolgensma^®), and the two recent gene therapy products for aromatic L-amino acid decarboxylase (AADC) deficiency, Kebilidi^® and Upstaza^®, which currently hold FDA and EMA approval, respectively. This review aims to highlight recent advances in the field of AAV gene therapy for neurological disorders, identify research gaps, and suggest areas for future investigation to enable potential breakthroughs particularly in neurodegenerative, neurodevelopmental, and neuromuscular disorders. We foresee that more tissue- and cell-specific AAV vectors designed using AI-powered platforms will emerge to precisely and efficiently target specific brain regions, transforming how CNS disorders are treated.