Intracellular delivery of full-length antibodies via organ-targeted lipid nanoparticles.

Abstract

Antibodies are proteins prized for their ability to bind to extracellular antigens with exceptionally high affinities and specificities. These features have motivated researchers to utilize antibody-antigen binding to inhibit intracellular disease targets in the proteome, yet delivery of antibodies into the cytosol of cells has long been a considerable challenge. Here, we outline the development of a lipid nanoparticle (LNP) platform for delivering antibodies into cells to selectively inhibit disease-relevant cytosolic targets. This approach efficiently delivers various therapeutic antibodies into multiple cancer cell lines, inhibiting key transcription factors in inflammatory and cancer signaling pathways. We further demonstrate systemic delivery of therapeutic antibodies in disease models, including α-synuclein-specific antibodies for Parkinson's disease and RelA-specific Immunoglobulins for acute lung injury using targeted LNP formulations. This work establishes a promising method for using LNPs for the delivery of antibody and antibody-derived therapeutics intracellularly to treat numerous proteome targets.