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arxiv; 2023.
Preprint in English | PREPRINT-ARXIV | ID: ppzbmed-2303.00288v2


mRNA therapy is gaining worldwide attention as an emerging therapeutic approach. The widespread use of mRNA vaccines during the COVID-19 outbreak has demonstrated the potential of mRNA therapy. As mRNA-based drugs have expanded and their indications have broadened, more patents for mRNA innovations have emerged. The global patent landscape for mRNA therapy has not yet been analyzed, indicating a research gap in need of filling, from new technology to productization. This study uses social network analysis with the patent quality assessment to investigate the temporal trends, citation relationship, and significant litigation for 16,101 mRNA therapy patents and summarizes the hot topics and potential future directions for this industry. The information obtained in this study not only may be utilized as a tool of knowledge for researchers in a comprehensive and integrated way but can also provide inspiration for efficient production methods for mRNA drugs. This study shows that infectious diseases and cancer are currently the primary applications for mRNA drugs. Emerging patent activity and lawsuits in this field are demonstrating that delivery technology remains one of the key challenges in the field and that drug-targeting research in combination with vector technology will be one of the major directions for the industry going forward. With significant funding, new organizations have developed novel delivery technologies in an attempt to break into the patent thicket established by companies such as Arbutus. The global mRNA therapeutic landscape is undergoing a multifaceted development pattern, and the monopoly of giant companies is being challenged.

Communicable Diseases , COVID-19 , Neoplasms
biorxiv; 2020.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2020.11.21.392407


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing an outbreak of coronavirus disease 2019 (COVID-19), has been undergoing various mutations. The analysis of the structural and energetic effects of mutations on protein-protein interactions between the receptor binding domain (RBD) of SARS-CoV-2 and angiotensin converting enzyme 2 (ACE2) or neutralizing monoclonal antibodies will be beneficial for epidemic surveillance, diagnosis, and optimization of neutralizing agents. According to the molecular dynamics simulation, a key mutation N439K in the SARS-CoV-2 RBD region created a new salt bridge which resulted in greater electrostatic complementarity. Furthermore, the N439K-mutated RBD bound hACE2 with a higher affinity than wild-type, which may lead to more infectious. In addition, the N439K-mutated RBD was markedly resistant to the SARS-CoV-2 neutralizing antibody REGN10987, which may lead to the failure of neutralization. These findings would offer guidance on the development of neutralizing antibodies and the prevention of COVID-19.

COVID-19 , Severe Acute Respiratory Syndrome
biorxiv; 2020.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2020.10.29.360479


Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. Systemic up-regulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19.

Lymphopenia , Carcinoma, Squamous Cell , COVID-19