Developing an extracellular vesicle-based nanoplatform for precision targeting of intraneuronal TDP-43

Impact Grant
Extracellular vesicles (EVs) are nanosized membrane enclosed vesicles secreted by all known types of cells. They are enriched with signature proteins from parental cells and carry a diverse range of cargos including DNA, RNA and proteins for the transmission of information from parent cell to recipient cell. In recent years, EVs have emerged as an exciting new class of drug delivery tool as they naturally overcome many limitations in brain drug delivery including cargo packaging, cell- and tissue-specificity, cellular internalisation and cargo release. They are regarded as a safer option than viral-based vectors and artificial nanoparticles due to low toxicity and immunogenicity of EVs. The overall goal of this study is to generate a EV-based platform to delivery MND therapeutics to affected cells. We will evaluate the delivery efficiency of EVs engineered with peptides and aptamers to enhance the specificity to affected neurons in cultured cells and in mice.