Researchers have successfully engineered Toxoplasma gondii, a parasite known for its ability to travel to the brain, to deliver therapeutic proteins to the brains of mice. This innovative approach overcomes the significant challenge of delivering macromolecular drugs across the blood-brain barrier, opening new avenues for treating neurological disorders.
The study, published in Nature Biotechnology, details how the research team targeted several proteins with varying sizes, functions, and target locations to the protein secretion organelles of T. gondii. They observed efficient delivery of these therapeutic proteins to neurons. The engineered parasite demonstrated the capability to deliver multiple proteins simultaneously, enhancing its potential for complex therapeutic interventions.
MeCP2 Delivery and Functional Impact
Focusing on MeCP2, a putative therapeutic target in Rett syndrome, the researchers further characterized their system. After delivering MeCP2 to brain organoids, they found that the protein bound to methylated DNA and altered the expression of known target genes. This indicates that the T. gondii delivered functional MeCP2 protein capable of exerting its intended biological effects.
Brain-Wide Protein Distribution in Mice
When the engineered parasite was used to deliver MeCP2 to the brains of mice, the protein distribution was widespread throughout the brain, with the highest levels observed in the cortex. This broad distribution suggests the potential for treating disorders affecting multiple brain regions.
