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SILENT: Stealth-Like Internalisation of Genetic Cargo for Ex vivo Natural Killer Cell Therapies

   School of Pharmacy

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  Dr Emma McErlean  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Natural killer (NK) cells are highly cytotoxic immune effectors and adoptive immunotherapy with NK cells has emerged as a promising treatment option for a variety of malignancies including carcinomas, myeloma, sarcomas, lymphomas and leukaemia. Genetic modification of immune cells with self-amplifying RNA (saRNA) is advantageous over non-amplifying mRNA due to lower dose requirements, which reduce the burden of manufacturing. Successful CAR-based immunotherapy requires an efficient transfer of the CAR transgene into the immune cells. Viral vectors are currently the transfection agent of choice for ex vivo cellular engineering. However, problems with safety concerns, expensive production and size limitations with genetic cargo warrants the development of novel non-viral delivery systems. NK cells are highly resistant to transfection by conventional non-viral methods such as electroporation and lipofection, and problems with toxicity and lower transfection rates have been well documented. The amphipathic peptide RALA (30 aa) and linear CHAT (15 aa) have been used to successfully deliver nucleic acids to a range of primary and cancer cell lines in vitro, without toxicity. The project will investigate, for the first time, novel peptides for stealth-like delivery of nucleic acids into NK cells for ex vivo cellular and adoptive therapies.

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