Engineering a Brain Parasite for Intracellular Delivery of Proteins to the Central Nervous System

Delivering macromolecules across biological barriers such as the blood-brain-barrier limits their application in vivo. Here we show that Toxoplasma gondii, a parasite that naturally travels from the human gut to the central nervous system (CNS) can be harnessed as a tool for protein delivery to the brain. We hijacked Toxoplasma's endogenous secretion systems to deliver multiple proteins-of-interest into neurons and characterize factors that affect delivery in brain organoids. We analyzed the transcriptional effects of protein delivery in human cortical brain organoids performing single cell transcriptomic profiling of infected and control organoids (Day 50).