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Computational-aided rational mutation design of pertuzumab to overcome active HER2 mutation S310F through antibody-drug conjugates.
Proc Natl Acad Sci U S A
January 2025
Laboratory of Precision Medicine and Biopharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.
View Article and Find Full Text PDFDevelopment and Validation of the Digital Sensitivity Scale for Adults: Cross-Sectional Observational Study.
J Med Internet Res
January 2025
Department of Psychiatry, Yongin Severance Hospital, Yongin, Republic of Korea.
Background: The COVID-19 pandemic has accelerated the digitalization of modern society, extending digital transformation to daily life and psychological evaluation and treatment. However, the development of competencies and literacy in handling digital technology has not kept pace, resulting in a significant disparity among individuals. Existing measurements of digital literacy were developed before widespread information and communications technology device adoption, mainly focusing on one's perceptions of their proficiency and the utility of device operation.
View Article and Find Full Text PDFA Susceptible Cell-Selective Delivery (SCSD) of mRNA-Encoded Cas13d Against Influenza Infection.
Adv Sci (Weinh)
January 2025
National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
To bolster the capacity for managing potential infectious diseases in the future, it is critical to develop specific antiviral drugs that can be rapidly designed and delivered precisely. Herein, a CRISPR/Cas13d system for broad-spectrum targeting of influenza A virus (IAV) from human, avian, and swine sources is designed, incorporating Cas13d mRNA and a tandem CRISPR RNA (crRNA) specific for the highly conserved regions of viral polymerase acidic (PA), nucleoprotein (NP), and matrix (M) gene segments, respectively. Given that the virus targets cells with specific receptors but is not limited to a single organ, a Susceptible Cell Selective Delivery (SCSD) system is developed by modifying a lipid nanoparticle with a peptide mimicking the function of the hemagglutinin of influenza virus to target sialic acid receptors.
View Article and Find Full Text PDFJourney of PROTAC: From Bench to Clinical Trial and Beyond.
Biochemistry
January 2025
Department of Chemistry, University of Illinois Chicago, Chicago, Illinois 60607, United States.
Proteolysis-targeting chimeras (PROTACs) represent a transformative advancement in drug discovery, offering a method to degrade specific intracellular proteins. Unlike traditional inhibitors, PROTACs are bifunctional molecules that target proteins for elimination, enabling the potential treatment of previously "undruggable" proteins. This concept, pioneered by Crews and his team, introduced the use of small molecules to link a target protein to an E3 ubiquitin ligase, inducing ubiquitination and subsequent degradation of the target protein.
View Article and Find Full Text PDFAntipsychotic off-label use in the 21st century: An enduring public health concern.
Dialogues Clin Neurosci
December 2025
University Bordeaux, Inserm, Bordeaux Population Health Research Center, Team Pharmacoepidemiology, UMR 1219, Bordeaux, France.
Soon after the introduction of second-generation antipsychotics, antipsychotic off-label use (OLU) progressively became a common prescribing practice. This evolving practice should be regularly monitored considering the growing number of persons exposed to the adverse effects of antipsychotics. The aim of the present review was to synthesise the literature published over the last 15 years on antipsychotic OLU for mental health symptoms.
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