DNA can be utilized as a generic delivery vector as well as a traditional biological material for DNA vaccination. Although the use of DNA as an antigen expression vector or a vaccine adjuvant has been intensively studied for several decades, the use of DNA molecules as a delivery carrier has not been explored until recently. This issue is probably due to the topological limitation of DNA in its natural linear or circular structure form. Multivalent DNA-based vector delivery platforms overcome this structural barrier and are particularly suited for DNA vaccine delivery because of their multifunctionality, monodispersity, anisotropicity, and bioconjugation ability with numerous functional moieties. In this chapter, we mainly describe the construction of multivalent DNA-based delivery vectors using DNA engineering methods. Specifically, the synthesis strategies for highly branched dendrimer-like DNA structures in general and methods for their application to DNA vaccine delivery are introduced.
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http://dx.doi.org/10.1007/978-1-4939-0410-5_11 | DOI Listing |
J Mater Chem B
December 2024
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
Biomolecular condensates (BCs) are crucial membraneless organelles formed through the process of liquid-liquid phase separation (LLPS) involving proteins and nucleic acids. These LLPS processes are tightly linked with essential cellular activities. Stress granules (SGs), functioning as cytoplasmic BCs, play indispensable roles in maintaining cellular homeostasis and are implicated in diseases like cancers and neurodegenerative disorders.
View Article and Find Full Text PDFChem Commun (Camb)
January 2025
School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, 511442, P. R. China.
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.
View Article and Find Full Text PDFNano Lett
November 2024
CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing 100190, China.
Nano Lett
September 2024
College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.
Lysosome-targeting chimera (LYTAC) shows great promise for protein-based therapeutics by targeted degradation of disease-associated membrane or extracellular proteins, yet its efficiency is constrained by the limited binding affinity between LYTAC reagents and designated proteins. Here, we established a programmable and multivalent LYTAC system by tandem assembly of DNA into a high-affinity protein degrader, a heterodimer aptamer nanostructure targeting both pathogenic membrane protein and lysosome-targeting receptor (insulin-like growth factor 2 receptor, IGF2R) with adjustable spatial distribution or organization pattern. The DNA-based multivalent LYTACs showed enhanced efficacy in removing immune-checkpoint protein programmable death-ligand 1 (PD-L1) and vascular endothelial growth factor receptor 2 (VEGFR2) in tumor cell membrane that respectively motivated a significant increase in T cell activity and a potent effect on cancer cell growth inhibition.
View Article and Find Full Text PDFACS Cent Sci
July 2024
Department of Chemistry, Emory University, Atlanta, Georgia 30322, United States.
Assays that detect viral infections play a significant role in limiting the spread of diseases such as SARS-CoV-2. Here, we present Rolosense, a virus sensing platform that leverages the motion of 5 μm DNA-based motors on RNA fuel chips to transduce the presence of viruses. Motors and chips are modified with aptamers, which are designed for multivalent binding to viral targets and lead to stalling of motion.
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