Systemic LNP-based delivery of mRNA into the brain (through BBB): Recent advances in lipid nanoparticle (LNP) technology enable systemic delivery of mRNA across the blood-brain barrier, offering promising therapeutic potential for glioblastoma and other central nervous system disorders. As shown in the attached publication in Science Advances (and similar ones below), incorporation of the serotonin (5-HT3) receptor ligand SR-57227 into ionizable lipids has been used to effectively facilitate brain-targeted mRNA delivery, which can be used to encode proteins like IL-12 for transient expression and/or genome/epigenome editors for long-lasting changes, highlighting significant implications for neurological disease treatment in the future. Original publication: https://lnkd.in/e6dBRTV3 Further reading: https://lnkd.in/eVCJfxmS https://lnkd.in/ekEkaD3E https://lnkd.in/ep-bYdeD https://lnkd.in/eNV2MNDv https://lnkd.in/eRCEA2JN
There is a nice recent webinar about this topic from Joshi Lab at Brigham and Women’s Hospital and Harvard Medical School: https://www.insights.bio/nucleic-acid-insights/webinars/722/targeting-brain-delivery-of-lipid-and-polymer-nanoparticlebased-gene-therapies-with-sunshine
An elaborate Trojan horse strategy for these unwieldy molecular Achaeans
Thanks for sharing, Lorenz. Unloading complete mRNA cargo will probably be the next big reveal..
This is a fantastic advance, and smart. I remain a bit concerned though as the ionizable lipid component is necessary for mRNA loading & release and also produces significant inflammation - something you really don't want in the brain. Targeting is half of the battle, now we need ionizable lipid components that still work well for delivery but have a reduced inflammatory profile.
💡 Great insight
The progress is impressive considering where we started not so long ago.
𝘊𝘰-𝘧𝘰𝘶𝘯𝘥𝘦𝘳, 𝘊𝘌𝘖 𝘚𝘵𝘦𝘢𝘭𝘵𝘩 𝘉𝘪𝘰𝘵𝘦𝘤𝘩
1wGreat progress, we might still need better specificity regarding various cell types in the brain, but looks like a nice distribution initially. On a different note, I see more and more papers with only Chinese names on it but the location is in the US. Wonder what is going on with the US education? Where is the push for diversity?