We present a versatile DNA-based LYTAC framework that allows control over the valency of chimeras and the distance between ligands through DNA self-assembly. By evaluating the degradation capabilities of LYTACs with 1, 3, and 9 valences, we confirm the broad applicability of the multivalent enhancement effect across different lysosome-targeting receptor-mediated degradation pathways. Our findings provide valuable insights into improving the degradation efficiency of LYTACs.
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http://dx.doi.org/10.1039/d4cc04842c | DOI Listing |
Virology
December 2024
Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Departamento de Biotecnología y Bioingeniería, Av. Instituto Politécnico Nacional 2508, Mexico City, 07360, Mexico; CINVESTAV, Programa de Doctorado Transdisciplinario en Desarrollo Científico y Tecnológico para la Sociedad, Mexico. Electronic address:
COVID-19 infections continue due to accessibility barriers to vaccines and the emergence of SARS-CoV-2 variants. An effective, safe, accessible, and broad-spectrum vaccine is still needed to control the disease. We developed a multivalent protein subunit vaccine comprising antigens designed from a non-N-glycosylated region of the receptor-binding domain of the spike protein of SARS-CoV-2.
View Article and Find Full Text PDFParasitol Res
December 2024
Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada.
Coccidiosis is caused by apicomplexan parasites of the genus Eimeria, which infect epithelial cells of the intestinal tract causing diarrhea and negatively impacting production in the poultry industry. The self-limiting and highly immunogenic nature of infection by Eimeria spp. make live vaccination an effective means of coccidiosis control.
View Article and Find Full Text PDFBiomacromolecules
December 2024
Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, United States.
The efficacy of tumor-targeted therapeutics, engineered to engage specific cellular receptors to promote accumulation and penetration, is strongly influenced by the carrier's affinity for its target and the valency of binding molecules incorporated into the carrier. Previous research has primarily focused on improving targeting by augmenting the number of binding proteins on the carrier, inadvertently raising avidity without isolating the individual effects of binding strength and valency. Herein, we precisely evaluate the impact of multivalency on tumor targeting with a recombinant approach to independently control valency, avidity, and size.
View Article and Find Full Text PDFJ Control Release
December 2024
Fralin Biomedical Research Institute at VTC, Virginia Tech, Roanoke, VA, USA; Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA, USA. Electronic address:
It has recently been recognized that the physical characteristics of biomaterials - such as size, structure, shape, charge, mechanical strength, hydrophobicity, and multivalency - regulate immunological functions in innate immune cells. In immuno-oncology applications, biomaterials are engineered with distinct physical properties to achieve desired innate immune responses. In this review, we discuss how physical characteristics influence effector functions and innate immune signaling pathways in distinct innate immune cell subtypes.
View Article and Find Full Text PDFPLoS Comput Biol
December 2024
Department of Bioengineering, University of California, Los Angeles, California, United States of America.
Systems serology aims to broadly profile the antigen binding, Fc biophysical features, immune receptor engagement, and effector functions of antibodies. This experimental approach excels at identifying antibody functional features that are relevant to a particular disease. However, a crucial limitation of this approach is its incomplete description of what structural features of the antibodies are responsible for the observed immune receptor engagement and effector functions.
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