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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (18)
Azmain Alamgir
Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University
Militsa Yaneva
Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University
Mor Sela
The Louis Family Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Department of Chemical Engineering, Technion–Israel Institute of Technology
Patricia Mora-Raimundo
The Louis Family Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Department of Chemical Engineering, Technion–Israel Institute of Technology
Haim Kadosh
The Louis Family Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Department of Chemical Engineering, Technion–Israel Institute of Technology
Souvik Ghosal
Department of Chemistry and Chemical Biology, Cornell University
Anas Odeh
Department of Genetics and Developmental Biology, The Rappaport Faculty of Medicine and Research Institute, Technion–Israel Institute of Technology
Yuval Richtman
The Louis Family Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Department of Chemical Engineering, Technion–Israel Institute of Technology
Neta Fibeesh
School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, Sagol School of Neuroscience, Tel University
Yael Leichtmann-Bardoogo
School of Biomedical Engineering, Engineering Faculty, Tel Aviv University
Ofir Sade
School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, Sagol School of Neuroscience, Tel University
Peleg Hasson
Department of Genetics and Developmental Biology, The Rappaport Faculty of Medicine and Research Institute, Technion–Israel Institute of Technology
Rory C. Chien
Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University
Uri Ashery
School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, Sagol School of Neuroscience, Tel University
Ben M. Maoz
School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, Sagol School of Neuroscience, Tel University
Avi Schroeder
The Louis Family Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Department of Chemical Engineering, Technion–Israel Institute of Technology
Matthew P. DeLisa
Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University
Christopher A. Alabi
Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University