title: Current Progress in Non-viral RNAi-Based Delivery Strategies to Lymphocytes.
abstract: RNAi-based therapy holds great promise, as it can be utilized for the treatment of multiple conditions in an accurate manner via sequence-specific manipulation of gene expression. To date, RNAi therapeutics have advanced into clinical trials for liver diseases and solid tumors; however, delivery of RNAi to leukocytes in general and to lymphocytes in particular remains a challenge. Lymphocytes are notoriously hard to transduce with RNAi payloads and are disseminated throughout the body, often located in deep tissues; therefore, developing an efficient systemic delivery system directed to lymphocytes is not a trivial task. Successful manipulation of lymphocyte function with RNAi possesses immense therapeutic potential, as it will enable researchers to resolve lymphocyte-implicated diseases such as inflammation, autoimmunity, transplant rejection, viral infections, and blood cancers. This potential has propelled the development of novel targeted delivery systems relying on the accumulating research knowledge from multiple disciplines, including materials science and engineering, immunology, and genetics. Here, we will discuss the recent progress in non-viral delivery strategies of RNAi payloads to lymphocytes. Special emphasis will be made on the challenges and potential opportunities in manipulating lymphocyte function with RNAi. These approaches might ultimately become a novel therapeutic modality to treat leukocyte-related diseases.
authors.affiliation: Laboratory of Precision NanoMedicine, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel; Department of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv 69978, Israel; Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv 69978, Israel; Cancer Biology Research Center, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Shoshy
authors.initials: S
authors.lastname: Mizrahy
authors.affiliation: Laboratory of Precision NanoMedicine, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel; Department of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv 69978, Israel; Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv 69978, Israel; Cancer Biology Research Center, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Inbal
authors.initials: I
authors.lastname: Hazan-Halevy
authors.affiliation: Laboratory of Precision NanoMedicine, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel; Department of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv 69978, Israel; Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv 69978, Israel; Cancer Biology Research Center, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Niels
authors.initials: N
authors.lastname: Dammes
authors.affiliation: Laboratory of Precision NanoMedicine, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel; Department of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv 69978, Israel; Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv 69978, Israel; Cancer Biology Research Center, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Dalit
authors.initials: D
authors.lastname: Landesman-Milo
authors.affiliation: Laboratory of Precision NanoMedicine, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel; Department of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv 69978, Israel; Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv 69978, Israel; Cancer Biology Research Center, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: peer@tauex.tau.ac.il.
authors.forename: Dan
authors.initials: D
authors.lastname: Peer
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000008:administration & dosage / Q000737:chemistry; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy; D002986:Clinical Trials as Topic; D050091:Dendrimers / Q000008:administration & dosage / Q000138:chemical synthesis; D016503:Drug Delivery Systems / Q000379:methods*; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy; D019337:Hematologic Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000737:chemistry; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D058990:Molecular Targeted Therapy / Q000379:methods*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy
chemical_list: D052157:Aptamers, Nucleotide; D050091:Dendrimers; D018796:Immunoconjugates; D034741:RNA, Small Interfering
keywords: RNAi; aptamer; drug delivery; lipid nanoparticles; lymphocytes