Medical Hypotheses, Год журнала: 2024, Номер unknown, С. 111491 - 111491
Опубликована: Сен. 1, 2024
Язык: Английский
Pathology - Research and Practice, Год журнала: 2025, Номер unknown, С. 155947 - 155947
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
1
Clinical Pharmacology & Therapeutics, Год журнала: 2025, Номер unknown
Опубликована: Март 14, 2025
The utilization of lipid nanoparticles (LNP) for encapsulating mRNA has revolutionized the field therapeutics, enabling rapid development COVID‐19 vaccines and cancer vaccines. However, clinical mRNA‐LNP therapeutics faces numerous challenges due to their complex mechanisms action limited experience. To overcome these hurdles, Model‐Informed Drug Development (MIDD) emerges as a valuable tool that can be applied facilitating evaluation safety efficacy through integration data from all stages into appropriate modeling simulation techniques. In this review, we provide an overview current MIDD applications in using vivo data. A variety methods are reviewed, including quantitative system pharmacology (QSP), physiologically based pharmacokinetics (PBPK), mechanistic pharmacokinetics/pharmacodynamics (PK/PD), population PK/PD, model‐based meta‐analysis (MBMA). Additionally, compare differences between mRNA‐based small interfering RNA, adeno‐associated virus‐based gene therapies terms pharmacology, discuss potential mutual sharing knowledge therapeutics. Furthermore, highlight promising future opportunities applying approaches drugs. By emphasizing importance throughout development, review aims encourage stakeholders recognize value its enhance
Язык: Английский
Процитировано
0
Journal of Controlled Release, Год журнала: 2025, Номер unknown, С. 113641 - 113641
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0
Cellular Oncology, Год журнала: 2025, Номер unknown
Опубликована: Апрель 22, 2025
Chimeric antigen receptor (CAR) therapy has successfully treated relapsed/refractory hematological cancers. This strategy can effectively target tumor cells. However, despite positive outcomes in clinical applications, challenges remain to overcome. These hurdles pertain the production of drugs, solid resistance, and side effects related treatment. Some cases have been missed during drug preparation due manufacturing issues, prolonged times, high costs. mainly arise from vitro process, so reevaluating this process could minimize number patients. The immune cells are traditionally collected sent laboratory; after several steps, modified express CAR gene before being injected back into patient's body. During vivo method, is introduced inside allows for treatment begin sooner, avoiding potential failures associated In review, we will elaborate on using CAR, examine benefits approach, ultimately present available solutions incorporating practice.
Язык: Английский
Процитировано
0
Advanced Healthcare Materials, Год журнала: 2025, Номер unknown
Опубликована: Май 6, 2025
Abstract Lipid nanoparticles (LNPs) have gained significant attention as effective nucleic acid delivery vehicles. Despite their success, LNPs are predominantly liver‐targeted which limits broader application. To expand the therapeutic potential of LNPs, this work implements a data‐driven approach that combines design experiments (DoE), high throughput screening (HTS), and machine learning (ML) to tailor LNP formulations for preferential immune cell targeting. This methodology involves generation 180 formulations, with varying lipid molar ratios chemistries, explore diverse space. aims identify properties enhance specificity while reducing hepatic uptake. The in vitro these provided rich dataset ML analysis, leading identification promising candidates improved cellular selectivity profiles. These findings validated vivo where it is demonstrated selected achieved spleen expression successful redirection tropism beyond cells. workflow highlights importance tailoring compositions development selective tropism.
Язык: Английский
Процитировано
0
Research, Год журнала: 2025, Номер 8
Опубликована: Янв. 1, 2025
Autoimmune kidney diseases (AIKDs) depict a range of disorders involving immune-mediated damage to the kidneys, where conventional biologic therapies monoclonal antibodies often prove insufficient because persistent autoreactive B cell reservoirs in lymphoid organs and inflammatory tissues. The appearance chimeric antigen receptor (CAR)-T targeting cells has shown transformative potential, with recent clinical trials showing remarkable efficacy anti-CD19 CAR-T achieving profound depletion, reducing immune complex deposition, ameliorating renal inflammation AIKDs. While these results highlight potential therapy facilitating reset overcoming treatment resistance, further investigations are imperative establish its long-term safety sustained therapeutic benefits. This review synthesizes current evidence on applications AIKDs, discusses critical considerations for translation, identifies existing limitations challenges, proposes strategic directions optimization advancement.
Язык: Английский
Процитировано
0
Nanotechnology, Год журнала: 2025, Номер 36(22), С. 222003 - 222003
Опубликована: Май 16, 2025
Abstract Chimeric antigen receptor T cells (CAR-T) immunotherapy has achieved remarkable progress in the treatment of hematological malignancies. However, it encounters challenges including complex manufacturing processes, high cost, and safety issues. Lipid nanoparticle (LNP) technology, as an advanced gene delivery platform, offers significant advancements to CAR-T therapy through its efficiency, low immunogenicity, safety. LNP enable vivo production cells, thereby improving reducing risks immunogenicity insertional mutations, simplifying process costs. The scalability rapid optimization ability position them promising candidates for cell production. technology is expected further promote development provide safer more economical options. Therefore, this paper aims a comprehensive systematic review application therapy. In review, we initially outline fundamental design, process, current Subsequently, present characteristics LNP, their advantages vectors, how they improve efficacy Finally, summarize research landscape applications This includes enhancing vitro transfection programming situ , facilitating T-cell activation, alleviating side effects therapy, combining with other immunotherapies. These will aid design mRNA systems based on promoting
Язык: Английский
Процитировано
0
Methods, Год журнала: 2025, Номер 241, С. 59 - 66
Опубликована: Май 21, 2025
The rapid advancement of RNA-based therapeutics, particularly in the wake COVID-19 vaccine success, has prompted significant research into optimizing RNA delivery mechanisms. This study evaluates NeoLNPTM Transfection Kit developed by Scindy Pharmaceutical, which utilizes lipid nanoparticles (LNPs) for efficient encapsulation and delivery. We systematically investigate various parameters affecting transfection efficiency, including concentration, RNA/LNP volume ratios, mixing techniques, LNP stability, culture media. Our results demonstrate that optimal concentration efficiency is around 40-60 ng/µL, with a 1:0.75-1:1 RNA-to-LNP ratio yielding highest protein expression. Additionally, we find gentle techniques outperform harsher methods, stability LNP-RNA complexes significantly influences outcomes. provides practical guidelines enhancing paving way more effective therapeutics.
Язык: Английский
Процитировано
0
Frontiers in Immunology, Год журнала: 2025, Номер 16
Опубликована: Май 29, 2025
While immunotherapy faces obstacles, the emergence of chimeric antigen receptor (CAR) engineered natural killer (NK) cells is paving new ways and might become a preferred option over CAR T very soon. NK introduce diverse cytotoxic mechanisms offering novel strategies to combat tumor resistance. Concurrently, improvements in cell homing gene-edited therapy offer promising avenues for overcoming challenges cancer immunotherapy. Our review addresses resistance engineering enhance functionality by improving migration sites, emphasizing insights from preclinical clinical studies.
Язык: Английский
Процитировано
0
Journal of Controlled Release, Год журнала: 2024, Номер 378, С. 170 - 194
Опубликована: Дек. 12, 2024
DNA-based therapies are often limited by challenges such as stability, long-term integration, low transfection efficiency, and insufficient targeted DNA delivery. This review focuses on recent progress in the design of non-viral delivery systems for enhancing modulation therapeutic efficiency. Cellular uptake intracellular trafficking mechanisms play a crucial role optimizing gene There two main strategies employed to improve efficiency vectors: (i) explore different administration routes (e.g., mucosal, intravenous, intramuscular, subcutaneous, intradermal, intratumoural, intraocular) that best facilitates optimal into cells organs (ii) modify vectors with cell-specific ligands natural ligands, antibodies, peptides, carbohydrates, or aptamers) enable specific higher specificity improved biodistribution. We describe how employing these is advancing field increasing clinical translation ultimate application therapies.
Язык: Английский
Процитировано
2