Our major research interest is to understand the biology and the function of extracellular vesicles (EVs) both in physiological and pathophysiological conditions. The aim is to develop a novel tool for disease diagnosis and treatment. Currently, we engineer EVs for visualization, monitoring and targeted-delivery of oligonucleotide therapeutics, including non-coding RNAs (microRNAs), DNAs, and CRISPR-Cas9 as well as low-molecular-weight drugs to develop an advanced therapeutic approach. The ultimate goal of our research is to translate basic scientific findings into clinical applications.
Vesicle release from cells or tissues into the extracellular space is an evolutionally conserved process. In recent years, these vesicles, such as exosomes and microvesicles termed Extracellular vesicles (EVs), became increasingly appreciated as an essential mechanism of cell-cell communication. EVs contain a wide range of biomolecules such as proteins, RNAs, and DNAs, which transfer these functional cargos to distant cells or tissues through circulation. Due to their increased stability in circulation, biocompatibility, low immunogenicity and toxicity, EVs are attractive diagnostic markers and delivery systems for therapeutics.
The Harada Lab uses genetic/cellular engineering tools to investigate EV biology, and to engineer EVs as a drug delivery cargo for oligonucleotide therapeutics and small molecular drugs.
Current research projects:
Targeted Epigenetic Therapy using Engineered EV-CRISPR/dCas9 system
One of the major challenges in gene therapy is targeted delivery. Using beta-cell targeting single-chain antibody labelled EVs as a delivery cargo of CRISPR/dCas9 epigenetic modulators, we aim to develop tools to alter epigenetic marks of specific genomic locus for inducing heritable genetic changes in pancreatic beta cells to treat type 1 diabetes.
EV mediated microRNA delivery for cancer therapy
MicroRNAs (miRNAs) are small endogenous non-coding RNA molecules that regulate gene expression in diverse biological processes. Some of the miRNAs can be a potent therapeutic target for specific type of cancers. Our lab is developing EV-miRNA mimic/inhibitor delivery system for epithelial tumors to study an efficacy of the miRNA treatment.
Development of “therapeutic guide proteins” using an in vivo EV-display screen
Biocompatibility feature of EVs makes an ideal carrier for in vivo targeting. We are developing an in vivo exosome-display screening strategy to select a “guide protein” expressed on the surface of naturally occurring cell-derived vesicles using the combination of scFv library screening and EV engineering.