Glycolipid nanoparticles target the spleen and detarget the liver without charge
Abstract
Lipid nanoparticles (LNPs) formulated with a neutral helper lipid can deliver RNA to the liver in humans. However, clinically relevant delivery to other tissues has remained challenging. To avoid the liver, scientists often add antibodies or helper lipids with a permanent charge. Here, we report an alternative approach: antibody- and charge-independent liver detargeting. Using DNA barcoding to test 109 chemically distinct LNPs in vivo, we found that replacing a neutral helper lipid with a neutral glycolipid reduced liver delivery and increased splenic delivery. Consistent with this differential tropism, these glycolipid nanoparticles caused differences in downstream cellular signaling in vivo compared to traditional LNPs. These data suggest that extrahepatic LNPs can be designed without the imposition of a net negative or positive charge.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (13)
Kara Gentry
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine
Liming Lian
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine
Hyejin Kim
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine
Ozgenur Celik
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine
Camille Jones
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine
Ananda R. Podilapu
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine
Avraham Shakked
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine
David Loughrey
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine
Ryan Zenhausern
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine
Bora Jang
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine
Jessie Doan
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine
Sebastian Rudden
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine
James E. Dahlman
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine