Abstract
The COVID-19 mRNA vaccine was developed by the scalable manufacture of lipid nanoparticles (LNPs) that encapsulate mRNA within the lipid. There are many potential applications for this large nucleic acid delivery technology, including the delivery of plasmid DNA for gene therapy. However, gene therapy for the brain requires LNP delivery across the blood-brain barrier (BBB). It is proposed that LNPs could be reformulated for brain delivery by conjugation of receptor-specific monoclonal antibodies (MAbs) to the LNP surface. The MAb acts as a molecular Trojan horse to trigger receptor-mediated transcytosis (RMT) of the LNP across the BBB and subsequent localization to the nucleus for transcription of the therapeutic gene. Trojan horse LNPs could enable new approaches to gene therapy of the brain.