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Systemic Modulation of Lymphocyte Subsets Using siRNAs Delivered via Targeted Lipid Nanoparticles

  • Inbal Hazan-Halevy
  • Daniel Rosenblum
  • Srinivas Ramishetti
  • Dan PeerEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1974)

Abstract

Systemic delivery of RNA interference (RNAi) payloads for manipulation of gene expression in lymphocytes holds a great potential as a novel therapeutic modality for hematological malignancies and autoimmune disorders. However, lymphocytes are among the most difficult cells to transfect with RNAi, as they are resistant to conventional transfection reagents and are dispersed throughout the body, making it a challenge to successfully deliver these payloads via systemic administration route. We have developed a strategy to target lymphocytes and deliver RNAi payloads in a cell-specific manner to induce therapeutic gene silencing. This approach utilizes antibodies that decorate lipid nanoparticle surfaces to home into lymphocyte subsets. This approach opens new avenues for discovery of new drug targets and potentially for therapeutics.

Keywords

RNA interference (RNAi) Gene silencing Small interfering RNAs (siRNAs) Lipid nanoparticles (LNPs) 

Notes

Acknowledgments

This work was supported in part by grants from the Dotan Hemato-oncology Center at Tel Aviv University, by the Lewis Trust for blood cancers and by the Leona M. and Harry B. Helmsley Nanotechnology Research Fund awarded to D.P.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Inbal Hazan-Halevy
    • 1
    • 2
    • 3
    • 4
  • Daniel Rosenblum
    • 1
    • 2
    • 3
    • 4
  • Srinivas Ramishetti
    • 1
    • 2
    • 3
    • 4
  • Dan Peer
    • 1
    • 2
    • 3
    • 4
    • 5
    Email author
  1. 1.Laboratory of Precision NanoMedicine, School of Molecular Cell Biology and BiotechnologyTel Aviv UniversityTel AvivIsrael
  2. 2.Department of Cell Research and Immunology, George S. Wise Faculty of Life SciencesTel Aviv UniversityTel AvivIsrael
  3. 3.Center for Nanoscience and NanotechnologyTel Aviv UniversityTel AvivIsrael
  4. 4.Cancer Biology Research CenterTel Aviv UniversityTel AvivIsrael
  5. 5.Department of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of EngineeringTel Aviv UniversityTel AvivIsrael

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