Programmable delivery of mitochondria to specific cell types
In this Tools of the Trade article, Ayupov (Roska lab) describes the development of MitoCatch, a method to display protein binders on the mitochondrial surface to facilitate cell-type-specific targeting during mitochondrial transplantation.
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Mitochondrial dysfunction contributes to the pathogenesis of a wide range of diseases, including neurodegenerative disorders such as Parkinson’s disease, optic neuropathies and conditions affecting other organs, including heart failure. Mitochondrial transplantation has emerged as a potential therapeutic strategy for these diseases. However, previous approaches have faced two major limitations: low efficiency and a lack of cell-type specificity, which have hindered its broad application and clinical translation.
To this end, we developed the MitoCatch technology, which enables the programmable, cell-type-specific delivery of mitochondria based on engineered protein binders. MitoCatch is based on three complementary strategies: targeting by binders displayed either on recipient cells (MitoCatch-C) or on donor mitochondria (MitoCatch-M), and through bispecific binders that bridge both mitochondrial and cellular surfaces (MitoCatch-Bi).