Red blood cell extracellular vesicles as robust carriers of RNA-based therapeutics
| Autor: | Alex Bai-Liang He, Yuen San Chan, Likun Wei, Ajijur Azad, Tin Chanh Pham, Luyen Tien Vu, Jiahai Shi, Ng Shyh-Chang, Siew Mei Chin, Mengsu Yang, Anskar Y.H. Leung, Boya Peng, Minh T.N. Le, Yuk Yan Kwok, Waqas Muhammad Usman, William C. Cho, Victor W.S. Ma |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Erythrocytes Physiology Cost effectiveness Genetic enhancement General Physics and Astronomy lcsh:Medicine Mice SCID chemistry.chemical_compound Biosafety Mice 0302 clinical medicine Drug Delivery Systems Red Blood Cells Guide RNA lcsh:Science lcsh:QH301-705.5 Cancer Multidisciplinary Chemistry Cell biology medicine.anatomical_structure 030220 oncology & carcinogenesis Drug delivery Molecular Medicine Female RNA Guide Kinetoplastida Biocompatibility Science Mice Nude Breast Neoplasms Therapeutics Biochemistry Genetics and Molecular Biology (miscellaneous) Extracellular vesicles General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Extracellular Vesicles Cell Line Tumor microRNA medicine Animals Humans Messenger RNA Oligonucleotide lcsh:R RNA General Chemistry Oligonucleotides Antisense medicine.disease Microreview Red blood cell MicroRNAs 030104 developmental biology lcsh:Biology (General) Nat lcsh:Q CRISPR-Cas Systems DNA Neoplasm Transplantation |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-15 (2018) Cell Stress Cell Stress, Vol 2, Iss 9, Pp 239-241 (2018) |
| ISSN: | 2041-1723 |
| Popis: | Most of the current methods for programmable RNA drug therapies are unsuitable for the clinic due to low uptake efficiency and high cytotoxicity. Extracellular vesicles (EVs) could solve these problems because they represent a natural mode of intercellular communication. However, current cellular sources for EV production are limited in availability and safety in terms of horizontal gene transfer. One potentially ideal source could be human red blood cells (RBCs). Group O-RBCs can be used as universal donors for large-scale EV production since they are readily available in blood banks and they are devoid of DNA. Here, we describe and validate a new strategy to generate large-scale amounts of RBC-derived EVs for the delivery of RNA drugs, including antisense oligonucleotides, Cas9 mRNA, and guide RNAs. RNA drug delivery with RBCEVs shows highly robust microRNA inhibition and CRISPR–Cas9 genome editing in both human cells and xenograft mouse models, with no observable cytotoxicity. |
| Databáze: | OpenAIRE |
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