mRNA based therapeutic / BioNTech, Bill & Melinda Gates Foundation - LARVOL DELTA

Understanding the impact of in vitro transcription byproducts and contaminants. (PubMed, Front Mol Biosci) - "The success of messenger (m)RNA-based vaccines against SARS-CoV-2 during the COVID-19 pandemic has led to rapid growth and innovation in the field of mRNA-based therapeutics...In addition, we briefly overview non-nucleotide-based contaminants such as RNases, endotoxin and metal ions that, when present in the IVT reaction, can also influence the activity of mRNA-based drugs. We further discuss current approaches aimed at adjusting the IVT reaction conditions or improving mRNA purification to achieve optimal performance for medical applications."

Journal • Preclinical • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Expression of the tumor antigens NY-ESO-1, tyrosinase, MAGE-A3, and TPTE in pediatric and adult melanoma: a retrospective case control study. (PubMed, Virchows Arch) - "BNT111, an investigational lipoplex-formulated mRNA-based therapeutic cancer vaccine encoding melanoma TAAs NY-ESO-1, tyrosinase, MAGE-A3, and TPTE, is undergoing clinical testing in adults. All four TAAs were expressed in pediatric melanoma, albeit NY-ESO-1 and MAGE-A3 to a lesser extent than in adult melanoma. These data support the possibility of investigating vaccines targeting these TAAs for the treatment of pediatric melanoma."

IO biomarker • Journal • Retrospective data • Cutaneous Melanoma • Melanoma • Oncology • Pediatrics • Solid Tumor • CTAG1B • Tyrosinase

Formation of dsRNA by-products during in vitro transcription can be reduced by using low steady-state levels of UTP. (PubMed, Front Mol Biosci) - " Low steady-state concentrations of UTP and GTP, fed in combination over the course of the in vitro transcription reaction, produce mRNA with high capping and low levels of dsRNA formation, resulting in high levels of protein expression. This novel approach may render laborious purification steps to remove dsRNA unnecessary."

Journal • Preclinical

Polysarcosine-Functionalized mRNA Lipid Nanoparticles Tailored for Immunotherapy. (PubMed, Pharmaceutics) - "Lipid nanoparticles (LNPs) have gained great attention as carriers for mRNA-based therapeutics, finding applications in various indications, extending beyond their recent use in vaccines for infectious diseases...Our study highlights the utility of pSar for improved mRNA LNP products and the importance of pSar as a novel stealth moiety enhancing efficiency in future LNP formulation development. SAXS can provide valuable information for the rational development of such novel formulations by elucidating structural features in different LNP compositions."

Journal • Infectious Disease • Oncology • THY1

mRNA-based therapies: Preclinical and clinical applications. (PubMed, Int Rev Cell Mol Biol) - "The value of IVT mRNA was recently proved during the COVID-19 pandemic when mRNA-based vaccines outperformed the efficacy of established technologies, and millions of doses were rapidly deployed. In this review, we will discuss chemical modifications of IVT mRNA and highlight numerous preclinical and clinical applications including vaccines for cancer and infectious diseases, cancer immunotherapy, protein replacement, gene editing, and cell reprogramming."

Journal • Preclinical • Immunology • Infectious Disease • Novel Coronavirus Disease • Oncology

Ribozyme Assays to Quantify the Capping Efficiency of In Vitro-Transcribed mRNA. (PubMed, Pharmaceutics) - "Using this technology, we determined the capping efficiencies of IVT mRNAs with different features, which include: Different cap structures, diverse 5' untranslated regions, different nucleoside modifications, and diverse lengths. Taken together, the ribozyme cleavage assays we developed are fast and reliable for the analysis of capping efficiency for research and development purposes, as well as a general quality control for mRNA-based therapeutics."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Oncology

pH-dependent behavior of ionizable cationic lipids in mRNA-carrying lipoplexes investigated by molecular dynamics simulations. (PubMed, Macromol Rapid Commun) - "Lipid-based nanoparticles and lipoplexes containing ionizable lipids in their formulation are among the most successful nanocarriers for mRNA-based therapies...We observe also that at high pH levels DODMA lipids undergo a gradual shift towards the hydrophobic part of the bilayer. This results in a significant increase of the leaflet-flipping rate of DODMA, a phenomenon which may ultimately affect the fusion process of the lipoplex with the endosomal membrane."

Journal