Houston Methodist Researchers Generate and Validate Humanized Biomimetic Nanovesicles to Target Neurons – Two Firsts in Nanovesicle Theranostics

Restoring neuronal function after degeneration, traumatic injury or neuroinflammation can make the difference between a chronic injury or disability and full recovery. Efforts in this field have been impeded by the inability to precisely target neural cells with therapeutics or diagnostics. Precision targeting of specific neurons could also alleviate off-target effects of these cargos, which would allow treatment or diagnosis without altering the brain microenvironment – a critical aspect of safe and effective neuronal disorder treatments. At Houston Methodist, researchers Francesca Taraballi, PhD, and Robert C. Krencik, PhD, are leading teams in a collaboration aimed at overcoming this obstacle to the treatment of brain disorders. Taraballi’s team is focused on “functionalizing” lipid based nanovesicles (NV) to target specific neuronal cell types. NVs are increasingly recognized as promising tools for delivery of diagnostics and therapeutics. Data indicates that surface engineering of NVs with membrane proteins from specific cell types increases NV biocompatibility and facilitates incorporation of functional attributes. This has been shown to work in other cell types, but Taraballi’s team is the first to try this approach with human neural cells for use within the nervous system. In order to get the nanovesicles “functionalized,” she needs Krencik’s team. Krencik has a novel, well-defined and scalable approach to generating human neural cells from skin-sourced induced pluripotent stem cells. He then takes membrane proteins from the lab-derived human neurons and places those human proteins onto the nanovesicles, thus humanizing them. Through those human membrane proteins, the NVs can interact more seamlessly with the neurons being targeted for treatment. This then increases the ability of the nanovesicles to deliver cargo into those neurons. Using Krencik’s approach, humanized lab-derived neural cells can be easily scaled up, facilitating increased efficiency compared to using non-human animal models and taking the uniqueness of human-specific cells into account

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