Mechanisms and optimization of endosomal escape for delivery applications

项目摘要/摘要 标题：用于细胞递送应用的内体逃逸的机制和优化 通过精确的细胞内生物递送来控制细胞的操纵 活性物质一直是探索细胞机制和治疗的长期目标 干预措施。然而，细胞递送是一个尚未解决的问题。多数 技术仍然效率低下，对细胞造成破坏，而且可能是有毒的。此外，没有单一的 该方法适用于所有大分子货物、跨细胞类型或在任何情况下(例如细胞 培养VS活体)。新出现的生物应用加剧了这个问题。 不断突破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 渗透细胞膜，能够精确控制实现这种细胞的分子 渗透性，并开发新的细胞递送平台。因此，拟议的研究将 大大促进了对细胞递送问题的理解和解决方案。

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.