Exosomes are the only bionormal nanovesicle and have high potential as a delivery vehicle for vaccines, biologics, and drugs. Our model of exosome biogenesis provides a unique roadmap for exosome engineering that allows us to produce exosome-based vaccines and therapeutics at high yield and potency, which we are developing in collaboration with other labs here at JHU and in the private sector.
Exosome Protein Engineering
We engineer proteins into exosomes by optimizing their (i) high-level expression, (ii) delivery to the plasma membrane, and (iii) loading into nascent budding vesicles. Discoveries in each of these areas allow us to rapidly produce exosomes carrying with nearly any protein of interest, including viral antigens and recombinant biologics, on the exosome surface or in the exosome lumen.
1. Maximizing the expression, endomembrane trafficking, and stability of exosome cargo proteins. Using gene editing technologies, we are creating genetically modified cell lines optimized for the synthesis, plasma membrane delivery, and exosomal secretion of recombinant proteins
2. Development of exosome-based vaccines for hepatitis C virus, hepatitis B virus, influenza, SARS-CoV-2 and other infectious agents. Here we design and build novel exosome-based vaccines, work with our collaborators to validate their potency, and interrogate their unique stimulatory effect on B-cell proliferation and antibody production.
3. Development of exosome-based therapeutics for combating pathogenic inflammation, aberrant angiogenesis, and cancer. Here we design exosomes that display high levels of cancer neoantigens and anti-cancer biologics, while also working with our collaborators to assess their in vitro and in vivo efficacy as cancer therapeutics.
Exosome RNA Engineering
Our team has invented technologies that load any RNA into exosomes at high efficiency. We are now combining these technologies with exosome-targeting modules for cell type-specific delivery of RNAs to the cells and tissues of greatest need
1. Inventing tissue-tropic exosomes. Our major goal is to develop tools and technologies that target exosomes to specific cells and tissues in target cells in vivo. This project involves decorating exosomes with peptides and proteins tropic for selected cell surface receptors, and to validate their cell type-specific tropism in vivo. These will then be combined with protein and RNA engineering to deliver vaccines and therapeutics to sites of disease in vivo.