ArticleNature microbiology2024
Engineering Toxoplasma gondii secretion systems for intracellular delivery of multiple large therapeutic proteins to neurons.
Article in Nature microbiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Micro-engineering the future.Nature microbiology · 2026Article
- Evaluation of Moringa oleifera extract and metal-organic frameworks (MOFs) as therapeutic agents against chronic Toxoplasma gondii infection in mice.Scientific reports · 2026Article
- Lessons on multicellular two- (2D) and three-dimensional (3D) culture in parasitology: Insights, challenges and future directions.International journal for parasitology · 2026Review
- Biomolecular Interfaces in Targeted Nano-Drug Delivery: Molecular Recognition, Signaling Modulation, and Translational Pathways.Biomolecules · 2026Review
- Toxoplasma gondii drives myeloid immune cell recruitment to amyloid plaques in Alzheimer's model mice.Journal of neuroinflammation · 2026Article
- Toxoplasma gondii as a drug for anti-tumor immunotherapy: mechanisms, challenges, and perspectives.Parasite (Paris, France) · 2026Review
- Bioinspired functional materials for biomedical applications.Frontiers in bioengineering and biotechnology · 2026Review
- Immunotherapy in central nervous system tumors.International journal of surgery (London, England) · 2025Review
- Comprehensive analysis of Toxoplasma gondii migration routes and tissue dissemination in the host.PLoS neglected tropical diseases · 2025Review
- Spatiotemporal Diffusion, Colonization, and Antibody Responses in Susceptible C57BL/6J Mice Orally Infected withVeterinary sciences · 2025Article
- The Advancements of Marine Natural Products in the Treatment of Alzheimer's Disease: A Study Based on Cell and Animal Experiments.Marine drugs · 2025Review
- Autonomous Nucleic Acid and Protein Nanocomputing Agents Engineered to Operate in Living Cells.ACS nano · 2025Review
- Human brain organoids: an innovative model for neurological disorder research and therapy.Frontiers in cellular neuroscience · 2025Review
- Central nervous system and immune cells interactions in cancer: unveiling new therapeutic avenues.Frontiers in immunology · 2025Review
- A year of microbiology.Nature microbiology · 2024Article
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28 authors.
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Abstract
Delivering macromolecules across biological barriers such as the blood-brain barrier limits their application in vivo. Previous work has demonstrated that Toxoplasma gondii, a parasite that naturally travels from the human gut to the central nervous system (CNS), can deliver proteins to host cells. Here we engineered T. gondii's endogenous secretion systems, the rhoptries and dense granules, to deliver multiple large (>100 kDa) therapeutic proteins into neurons via translational fusions to toxofilin and GRA16. We demonstrate delivery in cultured cells, brain organoids and in vivo, and probe protein activity using imaging, pull-down assays, scRNA-seq and fluorescent reporters. We demonstrate robust delivery after intraperitoneal administration in mice and characterize 3D distribution throughout the brain. As proof of concept, we demonstrate GRA16-mediated brain delivery of the MeCP2 protein, a putative therapeutic target for Rett syndrome. By characterizing the potential and current limitations of the system, we aim to guide future improvements that will be required for broader application.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.