Tools for translation: non-viral materials for therapeutic mRNA delivery

Hajj, Khalid A.; Whitehead, Kathryn A.

doi:10.1038/natrevmats.2017.56

Cited by 605 publications

(673 citation statements)

References 159 publications

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“…12, 18, 21, 22, 25, 26, 35 mRNA-based therapy possesses advantages over other nucleic acid-based approaches due to its endogenous translation process in the cytosol and no potential risk of genome mutagenesis. 15,28,32 However, the instability and insufficient translatability of mRNA remain a limitation to achieving maximized therapeutic windows.…”

Section: Introductionmentioning

confidence: 99%

Lipid Polymer Hybrid Nanomaterials for mRNA Delivery

Zhao

Zhang

et al. 2018

Cel. Mol. Bioeng.

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Introduction In the past decade, messenger RNA (mRNA) has been extensively explored in a wide variety of biomedical applications. However, efficient delivery of mRNA is still one of the key challenges for its broad applications in the clinic. Recently, lipid polymer hybrid nanoparticles (LPNs) are evolving as a promising class of biomaterials for RNA delivery, which integrate the physicochemical properties of both lipids and polymers. We previously developed an N1,N3,N5-tris(2-aminoethyl)benzene-1,3,5-tricarboxamide (TT) derived lipid-like nanomaterial (TT3-LLN) which was capable of effectively delivering multiple types of mRNA. In order to further improve the delivery efficiency of TT3-LLN, in this study, we focused on studying the effects of incorporating different polymers on establishing LPNs and aimed to develop an optimized lipid polymer hybrid nanomaterial for efficient mRNA delivery. Methods We incorporated a series of biodegradable and biocompatible polymer materials into the formulation of TT3-LLNs to develop LPNs. mRNA delivery efficiency of different LPNs were evaluated and a systematic orthogonal optimization was further carried out. Results Our data indicate that PLGA4 (MW 24,000–38,000 g/mol) dramatically increased delivery efficiency of TT3-LLNs in comparison to other polymers. Further optimization identified PLGA4–7 LPNs (PLGA:mRNA=9:1, mass ratio; TT3:DOPE:Cholesterol:DMG-PEG2000=25:25:45:0.75, molar ratio) as a lead formulation, which displayed significantly enhanced delivery of two types of mRNA in three different human cell lines as compared with TT3-LLNs. Conclusions Results from this study potentially provide new insights into developing LPNs for mRNA based therapeutics.

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Section: Introductionmentioning

confidence: 99%

Lipid Polymer Hybrid Nanomaterials for mRNA Delivery

Zhao

Zhang

et al. 2018

Cel. Mol. Bioeng.

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“…Through rational and individualized design, the synthetic mRNA should be closer to the natural mRNA while not affecting the therapeutic efficacy. In addition, the high cost of synthesized mRNA also limits its clinical application [13]. Continuing efforts are needed to develop more efficient synthesis methods of mRNA to reduce the production cost.…”

Section: Discussionmentioning

confidence: 99%

“…In parallel with these developments, nanotechnology has emerged as a promising method allowing these nucleic acids to withstand multiple extracellular and intracellular barriers (e.g., protecting them from enzymatic degradation, improving cytosolic transportation, and reducing renal filtration) [13–15]. The rise of mRNA nanomedicines is rapidly advancing their applications in a wide range of biomedical fields, such as vaccination, protein-replacement therapy, gene editing, and cell reprogramming and engineering.…”

Section: Introductionmentioning

confidence: 99%

Biomedical applications of mRNA nanomedicine

et al. 2018

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As an attractive alternative to plasmid DNA, messenger RNA (mRNA) has recently emerged as a promising class of nucleic acid therapeutics for biomedical applications. Advances in addressing the inherent shortcomings of mRNA and in the development of nanoparticle-based delivery systems have prompted the development and clinical translation of mRNA-based medicines. In this review, we discuss the chemical modification strategies of mRNA to improve its stability, minimize immune responses, and enhance translational efficacy. We also highlight recent progress in nanoparticle-based mRNA delivery. Considerable attention is given to the increasingly widespread applications of mRNA nanomedicine in the biomedical fields of vaccination, protein-replacement therapy, gene editing, and cellular reprogramming and engineering.

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“…Therefore, additional studies should be carried out to verify the link between digoxin synthesis and Zika virus infection. 12,13 Studies aimed at establishing a better understanding of immune responses to oncolytic viruses will be necessary to optimize the anti-glioma effects of oncolytic viruses 6 .…”

Section: Resultsmentioning

confidence: 99%

“…5 The potential therapeutic application of virus for the treatment of cancer is a mature concept and the aim is to induce the preferential viral infection in tumor cells and to minimize immunosuppressive responses in normal cells. 6,7 Glioblastoma has an annual incidence rate of 6 per 100,000 and accounts for about 27.5% of all primary brain tumors and 80% of all primary malignant brain tumors.8…”

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confidence: 99%

Potential Therapeutic Effect of Zika Virus in Glioblastoma Treatment

Nascimento

Santos

Alves

et al. 2018

AIMJ

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Abstract:Since the twentieth century, humanity has been experiencing a public health reality marked by numerous mosquito-borne diseases (belonging to the arthropod class), known as arboviruses. The Zika virus has become in recent years a risk to Brazilian and international public health due to its devastating effect due to its pathogenesis but also to fetal neurological development, causing serious health problems such as microcephaly and Guillain-Barré Syndrome, but also myelitis and meningoencephalitis. However, scientists studying the Zika virus have been trying to use the agent's ability to cause infections in healthy cells to attack and destroy cancer cells, such as the case of grade IV astrocytoma known as Gliobastoma Multiforme (GBM), which is a tumor of the very aggressive central nervous system and worse prognosis among primary cancers. As a result of effective therapy for GBM and the tropism of this etiological agent for brain cells, the hypothesis is that this virus would cause cell death in glioblastomas through metabolic alterations induced by the induced viral infection, but further studies must be carried out to demonstrate this therapeutic advantage in using the virus for the treatment of this malignant disease.

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Tools for translation: non-viral materials for therapeutic mRNA delivery

Cited by 605 publications

References 159 publications

Lipid Polymer Hybrid Nanomaterials for mRNA Delivery

Lipid Polymer Hybrid Nanomaterials for mRNA Delivery

Biomedical applications of mRNA nanomedicine

Potential Therapeutic Effect of Zika Virus in Glioblastoma Treatment

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