Targeted mRNA Delivery Using Bispecific Antibody-Lipid Nanoparticle Complexes

Area of Science:

• Biotechnology
• Nanomedicine
• Molecular Therapy

Background:

• Lipid nanoparticles (LNPs) are crucial for RNA therapeutics but face challenges in targeted extrahepatic delivery.
• Current LNP applications are limited for individualized therapies requiring specific cell enrichment.
• Novel platforms are needed for targeted LNPs with in vitro modeling capabilities before in vivo use.

Purpose of the Study:

• To develop and utilize a novel antibody-based targeting bispecific-LNP (TbsAb-LNP) platform.
• To enable targeted mRNA-LNP accumulation in specific cell types through simultaneous binding.
• To assess endosomal efficiency and in vitro/in vivo targeting capabilities.

Main Methods:

• Developed a TbsAb-LNP platform binding LNP polyethylene glycol motifs and cell surface markers.
• Colocalized TbsAb-LNPs with target cell surface markers for mRNA-LNP accumulation.
• Assessed endosomal efficiency kinetics and performed in vitro/in vivo targeting studies.

Main Results:

• Successfully achieved targeted delivery of TbsAb-LNPs to specific cell lines (xhuCD3, xmTfR1) in vitro.
• Demonstrated successful in vivo targeting of TbsAb-LNPs to xmTfR1-expressing cells.
• Observed enrichment of TbsAb-LNPs to splenic cells, indicating potential for vaccine and T-cell delivery.

Conclusions:

• The TbsAb-LNP platform offers a facile and modular approach for targeted LNP delivery.
• This platform overcomes limitations of complex chemical conjugation for LNP targeting.
• TbsAb-LNPs show significant potential for advancing clinical applications in vaccines and cell-specific therapies.