Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 27 for “"LNPs"”.
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Development and mechanistic analysis of in vivo liposomal nanoparticle delivery of siRNA and mRNA
… RNA to cells in vivo. Liposomal nanoparticles (LNPs) have shown some success, but their design is limited by both a lack of information concerning the optimal lipid composition and insufficient data regarding the LNPs' interaction with their environment. Further elucidation of the physical …
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The Impact of Lipid Nanoparticle Chemistry on RNA Delivery and Therapeutic Outcomes
… domain did not impact the formulation of 5A2-SC8 LNPs, including nanoparticle size, RNA encapsulation, and stability. However, the chemical structure did affect RNA delivery efficacy both in vitro and in vivo. The chemical structure of the hydrophobic domain of the PEG lipids impacted the escape …
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Development of high-throughput nanoparticle screening technologies to facilitate the delivery of genetic therapies to non-liver cell types
… is through the use of Lipid Nanoparticles (LNPs), due to their ease of manufacture and favorable toxicity profiles. Yet, LNPs have only seen clinical success as delivery methods to liver cells. In order to treat genetic diseases outside the liver, we hypothesized that a novel methodology for …
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Design, synthesis, and biological evaluation of diketopiperazine based ionizable lipids for the in vivo delivery of messenger RNA
… be overcome. Recently, lipid nanoparticles (LNPs) have shown promise for mRNA delivery in vivo, however, current leads are limited in terms of their efficacy, biodistribution, and toxicity. Here, we synthesize novel LNP delivery materials (i.e. ionizable lipids) that, when formulated into …
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Engineering Lipid Nanoparticle-Mediated Delivery of Nucleic Acids to Lymphoid Organs and Immune Cells
… delivery of nucleic acids. Lipid nanoparticles (LNPs) are an established essential platform for nucleic acid delivery. Efforts have led to the development of vaccines that protect against SARS-CoV-2 infection using LNPs to deliver mRNA coding for the viral spike protein. Significant challenges …
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Nanomaterials from lignocellulosic biomass : tailorable synthesis via surface functionalization and self-assembly mechanisms
… this work has the focus on lignin nanoparticles (LNPs) and lignin-containing cellulose nanofibrils (LCNFs). First, the lignin self-assembly in the formation of nanolignin was illustrated via combining the experimental data and the theoretical calculations. A modeling method applying …
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Elucidating the Impact of Endogenous Proteins on Lipid Nanoparticle Organ-Targeting Outcomes
… cell type(s). Presently, lipid nanoparticles (LNPs) represent the most clinically-advanced system for delivery of multiple classes of RNA, including small interfering RNA (siRNA), messenger RNA (mRNA), and guide RNAs for genome editing. Despite this progress, precise control of delivery to a …
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Design and synthesis of ionisable amino-polyester lipid nanoparticles for extrahepatic RNA delivery
… with lipids into nanoparticles (APE-LNPs) have demonstrated selective mRNA delivery to non-liver tissues. In the first part of this work, 36 ionisable APEs were synthesised to investigate how polymer composition affects APE-LNP physicochemical properties and mRNA delivery. The library …
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Nanoparticles Targeting at Inflammation Site
… and stability of lipid nanoparticles (LNPs) were enhanced through rational surface engineering. A comparative study between conventional PEG-lipids and zwitterionic peptide–lipid conjugates revealed that C(EK)₄-modified LNPs significantly improved membrane integrity and reduced …
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Optimization and analysis of lipid nanoparticles for in vivo mRNA delivery
… effective delivery vector. Lipid nanoparticles (LNPs) have shown considerable promise for the delivery of small interfering RNAs (siRNA) to the liver but their utility as agents for mRNA delivery have only been recently investigated. New delivery materials for mRNA delivery are also being …
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Tie-ing the endothelium: development of an mRNA-based nanotherapeutic to restore microvascular barrier function for the treatment of sepsis-induced multiple organ failure
… to degradation. Lipid nanoparticles (LNPs) containing ionizable cationic lipids emerged as the most clinically advanced platform for mRNA delivery, but their application for delivery to non-liver tissues is limited. Exploring alternatives to ionizable cationic lipids, such as ionizable …
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Granular Hydrogels for Localized Nanoparticle Delivery
… stabilizing and releasing lipid nanoparticles (LNPs) encapsulating nucleic acids for topical application. The approach builds upon glutathione–poly(ethylene glycol) (GSH–PEG) hydrogels previously designed for protein and small-molecule delivery. This work is based on the hypothesis that …
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Design and development of an RNA vaccine against tumor-mediated angiogenesis and metastasis targeting a KLH-Adrenomedullin fusion protein
… mRNA was encapsulated in lipid nanoparticles (LNPs) and injected in C57BL/6J mice. Empty LNPs were used as a negative control. After five immunizations, B16- F10 melanoma cells were injected through the tail vein to induce lung metastases. In addition, transgenic mice expressing green …
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Strategies for combinatorial development of siRNA conjugate delivery systems
… has been studied, including lipid nanoparticles (LNPs) and small molecule conjugates. LNPs are among the most potent and diverse nonviral delivery systems, and they have enjoyed continued improvement in efficacy as new generations of lipids have been explored. This steady progress in lipid …
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Understanding the intracellular signalling pathways activated by lipid nanoparticle delivery of mRNA
… (mRNA) therapies rely on lipid nanoparticles (LNPs) as delivery vehicles to transfect exogenously transcribed mRNA into cells for prophylactic or therapeutic use. LNP delivered mRNA (LNP/mRNA) in the clinic can induce a transient, innate immune response resulting in local and systemic …
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Engineered Type 1 Conventional Dendritic Cell–Based Therapies for In Situ Cancer Immunization
… With increased cDC1 population in tumors, Flt3L-LNPs enhanced T cell infiltration and modulated the immune environments in tumors and lymph nodes. Combination strategies using Flt3L-LNPs with immune checkpoint inhibitors and AC-NPs showed robust antitumor responses, achieving >50% tumor-free …
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Development of Extrachromosomal Genetic Technologies for Persistent and Tunable Expression of Therapeutic Payloads
… adenovirus (HC AdV), lipid nanoparticles (LNPs)—and by developing miniaturized systems with alternative tether protein DNA-binding domains, such as Tet Repressor (TetR) or Zinc Finger (ZF) proteins. Optimized EGTs will enable the production of persistent, tunable CGTs without disrupting the …
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Design of novel delivery systems to probe alternative routes of administration for a self-amplifying RNA rabies vaccine
… and, more specifically, lipid nanoparticles (LNPs) are efficient non-viral delivery systems for RNA and SAM vaccines. Within this thesis, a panel of cationic LNPs (cLNPs), based on existing cationic lipids (e.g. DOTAP and DDA), was designed to deliver a SAM vaccine. The rabies virus was used …
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RNA Therapeutics for Fibrolamellar Hepatocellular Carcinoma
… to FLC cells, I developed lipid nanoparticles(LNPs) based on the ionizable lipid C12-200. These LNPs effectively delivered mRNA encoding luciferase to cells in vitro, demonstrating their potential for delivering therapeutic RNA payloads. However, delivery to FLC cells in vivo remains …
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Novel Lipid Polymer Design for Nucleic Acids Delivery
… RNA (sgRNA)-Cas9 complexes. Lipid nanoparticles (LNPs) have emerged as one of the most successful non-viral carriers for nucleic acids, highlighted by the approval of the first small interfering RNA (siRNA) therapy and the rapid deployment of LNP-based mRNA vaccines against COVID-19. However, …
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