DEVELOPMENT OF CELLULAR DELIVERY TOOLS FOR BIOTECHNOLOGICAL AND THERAPEUTIC APPLICATIONS IN ANIMALS AND PLANTS
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Controlled manipulation of cells through the precise intracellular delivery of biologically active materials has been a long-term goal for biotechnological and therapeutic applications. Our ongoing research program aims to enable efficient delivery of macromolecules into animal or plant cells, through control of endosomal membrane permeability. Cellular delivery is 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. For example, effective macromolecular delivery would greatly amplify the therapeutic potentials of CRISPR-Cas9 technologies, wherein a large ribonucleoprotein complex provides challenges to current delivery systems, and of the manipulation of stem or immune system cells. We aim 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, our studies will significantly advance both understanding and solutions to the cell delivery problem. In turn, the new delivery tools developed as part of this research program will be useful to perform gene editing in plants or in animals, thereby enhancing agricultural competitiveness.