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LNP/mRNA therapeutics and AAV-based approaches require cell-level precision to achieve success without significant toxicity to other cells. To enable this, we developed SCP-Nano: an AI and tissue-clearing-based technology for precision nanotechnology. https://www.nature.com/articles/s41587-024-02528-1
LNP/mRNA therapeutics and AAV-based approaches require cell-level precision to achieve success without significant toxicity to other cells. To enable this, we developed SCP-Nano: an AI and tissue-clearing-based technology for precision nanotechnology. https://www.nature.com/articles/s41587-024-02528-1
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What is SCP-Nano?
A pipeline to map & quantify biodistribution of fluorescence-labeled nanocarriers in whole mouse bodies with single-cell resolution. It combines DISCO clearing, light-sheet microscopy, & deep learning.
Challenges SCP-Nano addresses:
Current methods like bioluminescence, PET, or MRI lack the resolution & sensitivity for low-dose nanocarrier applications like vaccines. SCP-Nano fills this gap with single-cell precision.
Tissue clearing innovations:
Existing clearing methods failed to preserve tagged mRNAs in nanocarriers. SCP-Nano optimized DISCO clearing by:
• Removing urea & sodium azide
• Reducing DCM exposure
Preserving fluorescence across the mouse body.
AI innovations:
Visualization is only step 1. Quantifying millions of targeted cells needs robust deep learning. We developed a pipeline delivering F1 scores >0.90, outperforming existing tools like Imaris.
Application 1:
Detailed delivery maps reveal organ-specific heterogeneity in LNP targeting, uncovering hotspots undetectable with traditional methods. Crucial for optimizing routes/doses.
Application 2:
Detect subtle off-target effects & assess molecular impacts via spatial proteomics. SCP-Nano ensures clinical safety & precision.