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WIREs Nanomed Nanobiotechnol
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Nanoscale platforms for messenger RNA delivery

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Messenger RNA (mRNA) has become a promising class of drugs for diverse therapeutic applications in the past few years. A series of clinical trials are ongoing or will be initiated in the near future for the treatment of a variety of diseases. Currently, mRNA‐based therapeutics mainly focuses on ex vivo transfection and local administration in clinical studies. Efficient and safe delivery of therapeutically relevant mRNAs remains one of the major challenges for their broad applications in humans. Thus, effective delivery systems are urgently needed to overcome this limitation. In recent years, numerous nanoscale biomaterials have been constructed for mRNA delivery in order to protect mRNA from extracellular degradation and facilitate endosomal escape after cellular uptake. Nanoscale platforms have expanded the feasibility of mRNA‐based therapeutics, and enabled its potential applications to protein replacement therapy, cancer immunotherapy, therapeutic vaccines, regenerative medicine, and genome editing. This review focuses on recent advances, challenges, and future directions in nanoscale platforms designed for mRNA delivery, including lipid and lipid‐derived nanoparticles, polymer‐based nanoparticles, protein derivatives mRNA complexes, and other types of nanomaterials. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology‐Inspired Nanomaterials > Lipid‐Based Structures Biology‐Inspired Nanomaterials > Nucleic Acid‐Based Structures
Structure of in vitro transcribed mRNA. Typically, mRNA consists of seven units including 5′ cap (ARCA, a representative cap), 5′ UTR, start codon (AUG), coding region, stop codon, 3′ UTR, and 3′ poly(A) tail
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Representative chemical structures of the main component of nanoparticles used for mRNA delivery in vivo
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Schematic diagram of intracellular mRNA delivery. Endogenous mRNA is transcribed from DNA, processed, and exported to cytoplasm for translation (red pathway). Alternatively, in vitro transcribed mRNA can be introduced into cytoplasm by nanoscale platforms (black pathway). Using exogenous mRNAs, functional proteins can be produced in the cytoplasm
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Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures
Biology-Inspired Nanomaterials > Lipid-Based Structures
Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

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