Engineering and intracellular delivery of recombinant antibodies

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AbstractsNontechnical Abstract:Antibodies are used as key tools for conducting biological research and are used as therapeutics for cancer, arthritis, and other conditions. While antibodies can be engineered to precisely target nearly any biological process, they cannot access the insides of cells, limiting their applications. A general strategy for introducing antibodies into cells would enable many new studies of how cells function and would also enable new therapies to be developed. This proposal will examine the key factors that will enable the introduction of antibodies into cells using a drug delivery strategy based on very small particles called nanoparticles. Because antibodies share a large number of common features, the specific work of this project is anticipated to lead directly to very broad applications in understanding how cells work and, in the long term, how to target processes that lead to disease initiation and progression. This project will support rigorous research training for graduate and undergraduate students at Tufts University. In addition, an expanded summer research program will provide opportunities for introducing area high school students to key concepts in the modern biotechnology industry, a rapidly growing portion of the local economy.Technical Abstract:Antibodies are key tools used in biological research that can be engineered to precisely interfere with individual signaling events, but intracellular applications of antibodies remain limited because of ongoing delivery challenges. This project will establish a general strategy for delivering antibodies intracellularly with the ultimate goal of targeted therapies for cancer and other diseases. To realize this approach, specific work to be conducted in this proposal will enable the elucidation of the molecular features that dictate effective antibody nanoparticle formulation, intracellular delivery, and interference with cell signaling. Because antibodies can be engineered to disrupt virtually any process of interest, this project will facilitate the establishment of general strategies for interfering with intracellular processes without the need for genetically modifying target cells. Robust strategies for intracellular antibody delivery have the potential to enable rapid exploration of therapeutic targets in a variety of diseases, including those targets traditionally viewed as "undruggable". The proposed work will train undergraduate, and graduate students in conducting rigorous scientific research in the areas of protein engineering and nanobiotechnology. In addition, expanding an existing summer research program to include a three-week Tufts Summer Camp for Protein Engineering and Nanomedicine (TUSC-PEN) will provide opportunities for introducing area high school students to key concepts in crucially important areas of the modern biotechnology industry.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.