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Engineered parasite delivers therapeutic proteins to the mouse brain

Engineered parasite delivers therapeutic proteins to the mouse brain

Science and Nature news

  • Research Highlight
  • Published: 13 September 2024

Drug delivery

Nature Biotechnology

volume 42, page 1357 (2024)Cite this article

Macromolecular drugs have limited applications in the brain because they cannot cross the blood–brain barrier. A parasite that does have the natural capacity to travel to the brain is Toxoplasma gondii. In a study in Nature Microbiology, Bracha et al. make use of this feature, engineering T. gondii to deliver large proteins to the brains of mice.

The authors targeted several proteins with different sizes, functions and target locations to the protein secretion organelles of T. gondii and tested their delivery to neurons, observing efficient delivery of various therapeutic proteins. The engineered T. gondii could also deliver multiple proteins simultaneously. The authors further characterized their system focusing on the delivery of MeCP2, which is a putative therapeutic target in Rett syndrome. After delivery to brain organoids, MeCP2 bound methylated DNA and altered the expression of known targets, indicating that T. gondii delivered functional MeCP2 protein. The engineered parasite was then used to deliver MeCP2 to the brains of mice. Protein delivery was distributed throughout the brain, with highest levels observed in the cortex.

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Author informationAuthors and Affiliations

  1. Nature Biotechnology https://www.nature.com/nbt/

    Iris Marchal

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Correspondence to
Iris Marchal.

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Cite this article

Marchal, I. Engineered parasite delivers therapeutic proteins to the mouse brain.
Nat Biotechnol 42, 1357 (2024). https://doi.org/10.1038/s41587-024-02399-6

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  • Published: 13 September 2024

  • Issue Date: September 2024

  • DOI: https://doi.org/10.1038/s41587-024-02399-6

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