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.
Title: Mechanisms and optimization of endosomal escape for cell delivery applications Reagents that can deliver proteins or nucleic acids inside live cells have the potential of revolutionizing the development of therapeutics for the treatment of human diseases. Currently, a major bottleneck in the field is that protein or nucleic acid therapeutics cannot penetrate cells efficiently. This project aims to solve this problem by developing reagents that make macromolecules cross membranes..
|Brock, Dakota J; Kustigian, Lauren; Jiang, Mengqiu et al. (2018) Efficient cell delivery mediated by lipid-specific endosomal escape of supercharged branched peptides. Traffic 19:421-435|
|Lian, Xizhen; Huang, Yanyan; Zhu, Yuanyuan et al. (2018) Enzyme-MOF Nanoreactor Activates Nontoxic Paracetamol for Cancer Therapy. Angew Chem Int Ed Engl 57:5725-5730|
|Lian, Xizhen; Erazo-Oliveras, Alfredo; Pellois, Jean-Philippe et al. (2017) High efficiency and long-term intracellular activity of an enzymatic nanofactory based on metal-organic frameworks. Nat Commun 8:2075|
|Najjar, Kristina; Erazo-Oliveras, Alfredo; Mosior, John W et al. (2017) Unlocking Endosomal Entrapment with Supercharged Arginine-Rich Peptides. Bioconjug Chem 28:2932-2941|
|Wang, Ting-Yi; Libardo, M Daben J; Angeles-Boza, Alfredo M et al. (2017) Membrane Oxidation in Cell Delivery and Cell Killing Applications. ACS Chem Biol 12:1170-1182|
|Libardo, M Daben J; Wang, Ting-Yi; Pellois, Jean-Philippe et al. (2017) How Does Membrane Oxidation Affect Cell Delivery and Cell Killing? Trends Biotechnol 35:686-690|
|Najjar, Kristina; Erazo-Oliveras, Alfredo; Brock, Dakota J et al. (2017) An l- to d-Amino Acid Conversion in an Endosomolytic Analog of the Cell-penetrating Peptide TAT Influences Proteolytic Stability, Endocytic Uptake, and Endosomal Escape. J Biol Chem 292:847-861|
|Wang, Ting-Yi; Pellois, Jean-Philippe (2016) Peptide translocation through the plasma membrane of human cells: Can oxidative stress be exploited to gain better intracellular access? Commun Integr Biol 9:e1205771|
|Robison, Aaron D; Sun, Simou; Poyton, Matthew F et al. (2016) Polyarginine Interacts More Strongly and Cooperatively than Polylysine with Phospholipid Bilayers. J Phys Chem B 120:9287-96|
|Wang, Ting-Yi; Sun, Yusha; Muthukrishnan, Nandhini et al. (2016) Membrane Oxidation Enables the Cytosolic Entry of Polyarginine Cell-penetrating Peptides. J Biol Chem 291:7902-14|
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