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: 10408003
• 负责人: Jean-Philippe Pellois
• 金额: $ 28.81万
• 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 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10408003
• 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; human disease; improved; in vivo; late endosome; macromolecule; nanoparticle; nucleic acid-based therapeutics; programs; rational design; 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/文摘

项目成果

Efficient and Innocuous Live-Cell Delivery: Making Membrane Barriers Disappear to Enable Cellular Biochemistry: How Better Cellular Delivery Tools Can Contribute to Precise and Quantitative Cell Biology Assays.

高效、无害的活细胞递送：使膜屏障消失以实现细胞生物化学：更好的细胞递送工具如何有助于精确和定量的细胞生物学测定。

• DOI: 10.1002/bies.201900031
• 发表时间: 2019
• 期刊: BioEssays : news and reviews in molecular, cellular and developmental biology
• 作者: Pellois,Jean-Philippe

In vivo peptide-based delivery of a gene-modifying enzyme into cells of the central nervous system.

• DOI: 10.1126/sciadv.abo2954
• 发表时间: 2022-09-30
• 期刊: SCIENCE ADVANCES
• 影响因子: 13.6
• 作者: Allen, Jason K.;Sutherland, Theresa C.;Prater, Austin R.;Geoffroy, Cedric G.;Pellois, Jean-Philippe
• 通讯作者: Pellois, Jean-Philippe

Efficient cell delivery mediated by lipid-specific endosomal escape of supercharged branched peptides.

• DOI: 10.1111/tra.12566
• 发表时间: 2018-06
• 期刊: Traffic (Copenhagen, Denmark)
• 作者: Brock DJ;Kustigian L;Jiang M;Graham K;Wang TY;Erazo-Oliveras A;Najjar K;Zhang J;Rye H;Pellois JP
• 通讯作者: Pellois JP

Mechanism of Cell Penetration by Permeabilization of Late Endosomes: Interplay between a Multivalent TAT Peptide and Bis(monoacylglycero)phosphate.

• DOI: 10.1016/j.chembiol.2020.07.015
• 发表时间: 2020-10-15
• 期刊: Cell chemical biology
• 影响因子: 8.6
• 作者: Brock DJ;Kondow-McConaghy H;Allen J;Brkljača Z;Kustigian L;Jiang M;Zhang J;Rye H;Vazdar M;Pellois JP
• 通讯作者: Pellois JP

Enzyme-MOF Nanoreactor Activates Nontoxic Paracetamol for Cancer Therapy.

• DOI: 10.1002/anie.201801378
• 发表时间: 2018-05-14
• 期刊: Angewandte Chemie (International ed. in English)
• 作者: Lian X;Huang Y;Zhu Y;Fang Y;Zhao R;Joseph E;Li J;Pellois JP;Zhou HC
• 通讯作者: Zhou HC