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      Delivering the right message: Challenges and opportunities in lipid nanoparticles-mediated modified mRNA therapeutics-An innate immune system standpoint.

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          Abstract

          mRNA molecules hold tremendous potential as a tool for gene therapy of a wide range of diseases. However, the main hurdle in implementation of mRNA for therapeutics, the systemic delivery of mRNA molecules to target cells, remains a challenge. A feasible solution for this challenge relies in the rapidly evolving field of nucleic acid-loaded nanocarriers and specifically in the established family of lipid-based nanoparticles (LNPs). Herein, we will discuss the main factors, which determine the fate of modified mRNA (mmRNA)-loaded LNPs in-vivo, and will focus on their interactions with the innate immune system as a main consideration in the design of lipid-based mmRNA delivery platforms.

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          Author and article information

          Journal
          Semin. Immunol.
          Seminars in immunology
          Elsevier BV
          1096-3618
          1044-5323
          December 2017
          : 34
          Affiliations
          [1 ] Laboratory of Precision NanoMedicine, Dept. of Cell Research & Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv 69978, Israel; Dept. of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv 69978, Israel; Center for Nanoscience and Nanotechnology, Tel Aviv 69978, Israel; Cancer Biology Research Center, Tel Aviv University, Tel Aviv 69978, Israel.
          [2 ] Laboratory of Precision NanoMedicine, Dept. of Cell Research & Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv 69978, Israel; Dept. of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv 69978, Israel; Center for Nanoscience and Nanotechnology, Tel Aviv 69978, Israel; Cancer Biology Research Center, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: peer@tauex.tau.ac.il.
          Article
          S1044-5323(17)30039-8
          10.1016/j.smim.2017.08.015
          28890238
          e50d5fb8-d492-48b7-94df-a0166232af16
          History

          mRNA,Lipid nanoparticles,Mononuclear phagocytic system,Pattern recognition receptors,RNA modifications,Systemic delivery

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