A Modular Platform for Targeted RNAi Therapeutics


Authors: R. Kedmi, N. Veiga, S. Ramishetti, M. Goldsmith, D. Rosenblum, N. Dammes, I. Hazan-Halevy, L. Nahary, S. Leviatan-Ben-Arye, M. Harlev, M. Behlke, I. Benhar, J. Lieberman and D. Peer

Journal: Nature Nanotechnology

DOI: 10.1038/s41565-017-0043-5

Publication - Abstract

January 29, 2018

Abstract:

Previous studies have identified relevant genes and signalling pathways that are hampered in human disorders as potential candidates for therapeutics. Developing nucleic acid-based tools to manipulate gene expression, such as short interfering RNAs (siRNAs), opens up opportunities for personalized medicine. Yet, although major progress has been made in developing siRNA targeted delivery carriers, mainly by utilizing monoclonal antibodies (mAbs) for targetingtheir clinical translation has not occurred. This is in part because of the massive development and production requirements and the high batch-to-batch variability of current technologies, which rely on chemical conjugation. Here we present a self-assembled modular platform that enables the construction of a theoretically unlimited repertoire of siRNA targeted carriers. The self-assembly of the platform is based on a membrane-anchored lipoprotein that is incorporated into siRNA-loaded lipid nanoparticles that interact with the antibody crystallizable fragment (Fc) domain. We show that a simple switch of eight different mAbs redirects the specific uptake of siRNAs by diverse leukocyte subsets in vivo. The therapeutic potential of the platform is demonstrated in an inflammatory bowel disease model by targeting colon macrophages to reduce inflammatory symptoms, and in a Mantle Cell Lymphoma xenograft model by targeting cancer cells to induce cell death and improve survival. This modular delivery platform represents a milestone in the development of precision medicine.

Advanced Search

close
  • Publications
  • Application Notes
  • Posters
  • Workshops
  • Videos & Webinars
  • Articles
Search

Browse by Category

  • Application
    • Diagnostic and Imaging
    • Genetic Medicine
    • Hematology
    • Metabolic Disorders
    • Neuroscience
    • Oncology
    • Skeletal Disorders
    • Targeted Drug Delivery
    • Vaccines
    • Other Applications
    • Cell therapy
  • Formulation
    • Liposomes
    • Nucleic Acid Lipid Nanoparticles
    • Polymeric Nanoparticles
    • Other Formulations
  • Payload
    • DNA
    • microRNA
    • mRNA
    • siRNA
    • Small Molecule Drugs
    • Other Payloads


related content

Publication - Summary

PTCD1 is Required for Mitochondrial Oxidative-phosphorylation: Possible Genetic Association with Alzheimer's Disease

D. Fleck, L. Phu, E. Verschueren, T. Hinkle, M. Reichelt, T. Bhangale, B. Haley, Y. Wang, R. Graham, D.S. Kirkpatrick, M. Sheng and B. Bingol

Using human genetic information and bioinformatics, Genentech have found a gene that is prominent in Azheimer’s Disease (AD) patients. In order to test molecular mechanism behind the gene's involvement in AD, they performed a functional study in rat neuronal cultures. Using...
Read More


Publication - Summary

Systemic Delivery of Factor IX Messenger RNA for Protein Replacement Therapy

S. Ramaswamy, N. Tonnu, K. Tachikawa, P. Limphong, J.B. Vega, P.P. Karmali, P. Chivukula, and I.M. Verma

Like most genetic disorders, Hemophilia B is caused by a mutation that leads to a dysfunctional protein. Hemophilia B patients are susceptible to life threatening bleeds when injured due to a clotting defect caused by a mutated coagulation fac...

Read More


Sign Up and Stay Informed
Sign up today to automatically receive new Precision NanoSystems application notes, conference posters, relevant science publications, and webinar invites.