Mechanisms and optimization of endosomal escape for delivery applications

递送应用的内体逃逸机制和优化

• 批准号: 10158494
• 负责人: Jean-Philippe Pellois
• 金额: $ 28.9万
• 依托单位: TEXAS A&M AGRILIFE RESEARCH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10158494
• 关键词: Biological; CRISPR/Cas technology; Capsid; Cations; Cell Culture Techniques; Cell Membrane Permeability; Cell Nucleus; Cells; Cellular Membrane; Chemicals; Complex; Cytosol; Data; Development; Enzymes; Extravasation; Funding; Genes; Goals; Human; Immune; Immune system; Learning; Lipids; Liposomes; Macromolecular Complexes; Mediating; Membrane; Membrane Biology; Methods; Modeling; Molecular; Molecular Probes; Nature; Nucleic Acids; Pathway interactions; Penetration; Peptides; Polymers; Problem Solving; Process; Proteins; Reagent; Research; Resistance; Ribonucleoproteins; Surface; System; Techniques; Therapeutic; Therapeutic Intervention; Toxic effect; Viral; Virus-like particle; Work; bis(monoacylglyceryl)phosphate; cell type; density; design; human disease; improved; in vivo; late endosome; macromolecule; nanoparticle; nucleic acid-based therapeutics; programs; response; small molecule; stem; synergism; therapeutic development; trafficking; transcription factor; uptake

PROJECT SUMMARY/ABSTRACT Title: Mechanisms and optimization of endosomal escape for cell delivery applications Controlled manipulation of cells through the precise intracellular delivery of biologically active materials has been a long-term goal for probing of cellular mechanisms and therapeutic interventions. Cellular delivery is however a problem that has not yet been solved. Most techniques remain inefficient, are disruptive to cells and can be toxic. Furthermore, no single approach works for all macromolecular cargo, across cell types, or in every context (e.g. cell cultures vs in vivo). This problem is exacerbated by emerging biological applications continually pushing the boundaries of required delivery efficiencies and versatility (e.g. CRISPR-Cas9 technologies). This project aims to reveal fundamental mechanisms of how to permeate cellular membranes, enabling precise control of the molecules that achieve this cell permeation, and to develop new platforms for cellular delivery. Thus, the proposed studies will significantly advance both understanding and solutions to the cell delivery problem.

项目总结/摘要 标题：用于细胞递送应用的内体逃逸的机制和优化 通过精确的细胞内递送生物学活性物质来控制细胞操作 活性材料一直是探索细胞机制和治疗的长期目标。 干预措施。然而，蜂窝递送是一个尚未解决的问题。最 这些技术仍然效率低下，对细胞具有破坏性，并且可能是有毒的。此外，没有一个 一种方法适用于所有大分子货物，跨细胞类型，或在每种情况下（例如细胞 培养物与体内）。这一问题因新兴的生物应用而加剧 不断推动所需交付效率和多功能性的界限（例如， CRISPR-Cas9技术）。该项目旨在揭示如何在 渗透细胞膜，使精确控制的分子，实现这一细胞 渗透，并开发用于细胞递送的新平台。因此，拟议的研究将 显著地推进了对细胞递送问题的理解和解决方案。