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A Versatile Antibody Capture System that Drives Precise In Vivo Delivery of mRNA loaded Lipid Nanoparticles and Enhances Gene Expression

Chen, M.; Yuen, D.; McLeod, V. M.; Yong, K. W.; Smyth, C. H.; Rossi Herling, B.; Payne, T.; Fabb, S.; Belousoff, M. J.; Algarni, A.; Sexton, P. M.; Porter, C. J. H.; Pouton, C. W.; Johnston, A. P. R.

2024-08-08 bioengineering
10.1101/2024.08.07.607101 bioRxiv
Show abstract

Efficient and precise delivery of mRNA is critical to advance mRNA therapies beyond their current use as vaccines. Lipid nanoparticles (LNP) efficiently encapsulate and protect mRNA, but non-specific cellular uptake may lead to off-target delivery and minimal delivery to target cells. Functionalizing LNPs with antibodies enables targeted mRNA delivery, but traditional modification techniques require complex conjugation and purification, which often reduces antibody affinity. Here, we present a simple method for capturing antibodies in their optimal orientation on LNPs, without antibody modification or complex purification. This strategy uses an optimally oriented anti-Fc nanobody on the LNP surface to capture antibodies, resulting in protein expression levels >1000 times higher than non-targeted LNPs and >8 times higher than conventional antibody functionalization techniques. These precisely targeted LNPs showed highly efficient in vivo targeting to T cells, with minimal delivery to other immune cells. This approach enables the rapid development of targeted LNPs and has the potential to broaden the use of mRNA therapies.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.