Nuevas estrategias biocatalíticas para la obtención de moléculas de interés en la industria farmaceútica: diltiazem

La estrategias de síntesis de compuestos farmacológicos o químicos han ido cambiando con el desarrollo de la ciencia. En este ámbito, la biocatálisis ha supuesto un gran avance en la obtención de moléculas de interés para la industria farmacéutica. Gracias a todas sus ventajas, entre las que destaca el cumplimiento de los 12 principios de la Química Verde o Química Sostenible, está en continuo crecimiento. Una de las moléculas obtenidas gracias a esta metodología es el diltiazem, fármaco perteneciente al grupo de los antagonistas de calcio, utilizado para tratar las arritmias, entre otras patologías. Las enfermedades cardiovasculares suponen un importante reto en cuanto a su tratamiento se refiere, pues el número de personas con patologías de este tipo, como infarto de miocardio, hipertensión arterial o arritmias, aumenta con el paso de los años. Como dato, las enfermedades cardiovasculares y el cáncer son la principal causa de muerte en los países desarrollados. Este trabajo se centra en la explicación detallada de la reacción biocatalítica llevada a cabo para sintetizar el diltiazem. Se revisa el tipo de reacción y las enzimas utilizadas para ello, así como el fundamento tanto químico como biotecnológico. Se abordan además los 12 principios de la Química Verde, y cómo la biocatálisis contribuye a la sostenibilidad

Development of a new mRNA vaccine platform for tuberculosis

Background Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), is the frst cause of death by an infectious disease worldwide, killed 1.6 million people in 2021. Bacillus Calmette-Guerin (BCG) is the only approved vaccine for TB to date. However, while BCG is efective in preventing severe forms in children, its efcacy in adults is inconsistent and it does not prevent transmission, highlighting the need for new vaccine development [1]. The recent success of COVID-19 vaccines raised the interest for mRNA-based vaccines, as they are efective, safe and easy to produce. This project aims to develop a new mRNA vaccine platform for TB, based on mRNA coding for antigenic peptides from BCG and M.tb identifed by immunopeptidomics [2], and formulated with a patented technology of lipid nanoemulsions (NE) (WO2019138139A1), adapted for efcient intracellular delivery of mRNA [3]. Materials and methods We tested diferent prototypes of NE-mRNA formulations, coding for EGFP, in vitro. Human alveolar basal epithelial cells (A549), human monocytic cells (THP-1), and primary human monocyte-derived macrophages, were transfected with NE-mRNA formulations. Transfection efciency was assessed by measuring the percentage of transfected cells, and the intensity of GFP fuorescence. The cytotoxicity of the formulations was evaluated using AlamarBlue, and by 7-AAD viability staining. Results In vitro preliminary data using EGFP-mRNA-NE formulations indicate that NE formulations can efciently deliver mRNA and induce expression of the encoded protein in diferent cell types, with low cytotoxicity. Conclusions The NE technology presented here is safe, stable, and can efciently deliver mRNA to various cell types. Selected NE formulations will be used as a carrier for a new vaccine candidate against TB, based on mRNA encoding relevant antigenic peptides. These will be tested in mice for safety, immunogenicity, efcacy and dose optimization in order to generate an efective and sustained humoral and cellular immune response against TB. The mRNA vaccines are rapid and relatively simple to produce. The vaccine platform described here could be adapted to develop vaccines against other infectious diseases, particularly to quickly respond to emerging pathogens.info:eu-repo/semantics/publishedVersio

The Potential of Nanomedicine to Unlock the Limitless Applications of mRNA

The year 2020 was a turning point in the way society perceives science. Messenger RNA (mRNA) technology finally showed and shared its potential, starting a new era in medicine. However, there is no doubt that commercialization of these vaccines would not have been possible without nanotechnology, which has finally answered the long-term question of how to deliver mRNA in vivo. The aim of this review is to showcase the importance of this scientific milestone for the development of additional mRNA therapeutics. Firstly, we provide a full description of the marketed vaccine formulations and disclose LNPs’ pharmaceutical properties, including composition, structure, and manufacturing considerations Additionally, we review different types of lipid-based delivery technologies currently in preclinical and clinical development, namely lipoplexes and cationic nanoemulsions. Finally, we highlight the most promising clinical applications of mRNA in different fields such as vaccinology, immuno-oncology, gene therapy for rare genetic diseases and gene editing using CRISPR Cas9

New mRNA - nanoemulsions vaccine platform: application for Tuberculosis vaccine development

Background: Tuberculosis (TB) is a deadly infectious disease caused by the airborne bacterium Mycobacterium Tuberculosis (M.tb), killing 1.6 million people every year, especially in low- and middle-income countries. The only licensed TB vaccine, a live attenuated strain of M. bovis (BCG), has variable efficacy, does not prevent transmission and is not safe in immunocompromised patients, particularly AIDS patients, who are at high risk of developing TB disease. Thus, the development of an efficient, safe and cost-effective tuberculosis vaccine remains a research priority. mRNA vaccine technology, which proved its potential during the COVID-19 pandemic, could represent a valuable alternative to conventional vaccines against TB. Objectives: We aim to establish a novel vaccine platform against TB, combining antigen identification by immunopeptidomics, mRNA design and production using advanced techniques, and a patented technology of lipid nanoemulsion (NE) adapted to efficiently deliver mRNA to target cells. Methods: Using a prototype mRNA encoding the fluorescent protein EGFP, we assessed in vitro the safety and transfection efficiency of different NE formulations on human alveolar basal epithelial cells (A549) and primary human monocyte-derived macrophages and dendritic cells. Results: Here we show that NEs can efficiently deliver mRNA to different cell types without significant cytotoxicity, and the formulation can be tailored to increase uptake by specific cells relevant for vaccination applications. Conclusion: Lipid NEs appear to be safe, easily adaptable and efficient transporters for mRNA. We will use selected NE formulations as carriers for mRNA vaccine candidates encoding relevant antigenic peptides from M.tb and other Mycobacterium species. Safety and immunogenicity studies will be performed in mice and the vaccination schedule will be optimized to generate a sustained humoral and cellular immune response against TB. This vaccine platform could be adapted to develop vaccines against other infectious diseases, particularly to quickly respond to emerging pathogens.info:eu-repo/semantics/publishedVersio