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Tools for translation: non-viral materials for therapeutic mRNA delivery
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In the citing paper
“To maximize translation, the mRNA sequence typically incorporates modified nucleosides, such as pseudouridine, N1-methylpseudouridine or other nucleoside analogues23.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [23]
In the citing paper
“mRNA has shown therapeutic potential in a range of applications, including viral vaccines, protein replacement therapies, cancer immunotherapies, cellular reprogramming and genome editing2,4,7–17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [7]
In the citing paper
“These lipids can improve nanoparticle properties, such as particle stability, delivery efficacy, tolerability and biodistribution7,14,17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [7]
In the citing paper
“Trapped in endosomes, in which the pH is lower than in the extracellular environment, ionizable lipids are protonated and, therefore, become positively charged, which may promote membrane destabilization and facilitate endosomal escape of the nanoparticles7,11,14”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [7]
In the citing paper
“To function in vivo, lipid nanoparticle–mRNA formulations need to overcome multiple extracellular and intracellular barriers7,11 (Fig. 3a).”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [7]
In the citing paper
“In addition to cationic or ionizable lipids, lipid nanoparticle–mRNA formulations typically contain other lipid components, such as phospholipids (for example, phosphatidylcholine and phosphatidylethanolamine), cholesterol or polyethylene glycol (PEG)-functionalized lipids (PEG-lipids)7,14,17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [7]
In the citing paper
“The pH-sensitivity of ionizable lipids is beneficial for mRNA delivery in vivo, because neutral lipids have less interactions with the anionic membranes of blood cells and, thus, improve the biocompatibility of lipid nanoparticles7,11,14.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [7]
In the citing paper
“mRNA normally contains five structural elements, that is, a 5′ cap, a 3′ poly(A) tail, a protein-coding sequence and 5′ and 3′ untranslated regions (UTRs)2,4,7,13.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [7]
In the citing paper
“These elements can be engineered to improve the stability and translational efficiency of mRNA2,4,7,13.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [7]
In the citing paper
“Chemical modifications of specific IVT mRNA nucleotides, such as pseudouridine (ψ) and N1-methylpseudouridine (m1ψ), can reduce innate immune sensing of exogenous mRNA translation2,4,7,182.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [7]
In the citing paper
“Chromatographic purification can remove double-stranded RNA, an analogue of viral genome, in IVT mRNA preparations, diminishing immune activation and increasing translational efficiency2,4,7,183.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [7]
In the citing paper
“To address these concerns, the engineering of mRNA molecules (Box 1) and the design of lipid nanoparticles have been optimized2,4,7–17, which has contributed to the rapid development and clinical assessment15,17 of the two COVID-19 mRNA vaccines, mRNA-1273 (NCT04470427)19,20 and BNT162b2 (NCT04368728)21.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [7]
In the citing paper
“Polymers, such as polyethyleneimine, protamine and polyaspartamide derivatives, are already widely used for mRNA delivery7–17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [7]
In the citing paper
“mRNA functions as the bridge between DNA and proteins in eukaryotic cells.[8, 12, 119]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [8]
In the citing paper
“Polyethylenimine (PEI) is one of the most developed cationic polymers [39], but its toxicity has limited the therapeutic applications.[8, 124]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [8]
In the citing paper
“Compared with protein drugs, mRNA can supplement both cytoplasmic and large transmembranic proteins.[8, 119, 120]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [8]
In the citing paper
“Recently, many biomaterials have been developed for mRNA delivery, including lipids and lipid derived materials, polymers, and many others. [8, 39, 120, 124]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [8]
In the citing paper
“Relative to plasmid DNA (pDNA), mRNA possesses temporary bioactivity and functions outside the nucleus, leading to a more controllable protein expression and avoiding the potential insertion of the genome.[8, 119, 120]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [8]
In the citing paper
“For many GARDs, the liver is a preferred organ for mRNA-based PRTs because systemically administrated mRNA vehicles are predominantly trapped by the reticuloendothelial system (RES) in the liver.”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [8]
In the citing paper
“In addition, the interaction between apolipoprotein E (apoE) and biomaterials such as lipid and lipid derived materials facilitates the accumulation in the liver.[8, 18, 34, 39, 59, 120, 121, 124, 164, 165]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [8]
In the citing paper
“Meanwhile, ionizable lipid and lipid derived materials, which acquire positive charges at low pH and become neutral at physiological pH, have been developed for decreasing the toxicity and immunogenicity while retaining the delivery efficiency.[8]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [8]
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“Furthermore, to enhance in vivo stability and delivery efficiency, these systems are often further modified with PEG or conjugated with specific targeting ligands for surface functionalization [148, 149].”
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“17–19 The FDA has approved two intramuscular (i.m.)-delivered, LNP-based mRNA vaccines for coronavirus (COVID-19) 20,21 and LNP-mediated systemic delivery of siRNA for the treatment of hereditary transthyretin amyloidosis, 22 demonstrating the clinical impact and feasibility of an LNP-based…”
Development of a Library of Disulfide Bond-Containing Cationic Lipids for mRNA Delivery
Shen, Z., Liu, C., Wang, Z., Xie, F., Liu, X., Dong, L., Pan, X., Zeng, C., & Wang, P. G. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020477 · Cited by 17
“During the past decade, a variety of non-viral mRNA delivery vehicles have emerged, such as lipid nanoparticles (LNPs) [17], polymers [18] and inorganic nanoparticles [19].”
BackgroundDelivery of mRNA for cancer therapy: progress and prospects
Su, L.-J., Xu, M.-X., Ji, Z.-H., Zhu, J.-Q., Yu, M., Wang, Y., & Lin, Y. (2023) · Nano Today · doi:10.1016/j.nantod.2023.102013 · Cited by 17
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Mechanistic modeling of lipid nanoparticle formation for the delivery of nucleic acid therapeutics
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Progress in cancer vaccines enabled by nanotechnology
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Intracellular delivery of messenger RNA to macrophages with surfactant-derived lipid nanoparticles
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mRNA therapy for myocardial infarction: A review of targets and delivery vehicles
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“Ionizable lipid nanoparticles are developed to overcome the limitations of cationic lipids (Meng et al., 2000; Hajj and Whitehead, 2017).”
BackgroundQin, S., Huang, H., Xiao, W., Chen, K., He, X., Tang, X., Huang, Z., Zhang, Y., Duan, X., Fan, N., et al. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.01.010 · Cited by 16
“Ionizable lipids are pH-sensitive and can be protonated to be positively charged or electrically neutral at physiological pH, which improves their biocompatibility and in vivo delivery efficiency 79 e 81 .”
BackgroundOptimal delivery strategies for nanoparticle-mediated mRNA delivery
Li, X., Guo, X., Hu, M., Cai, R., & Chen, C. (2023) · Journal of Materials Chemistry B · doi:10.1039/d2tb02455a · Cited by 16
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The global patent landscape of mRNA for diagnosis and therapy
Lyu, M., Chen, J., Peng, Y., Han, F., Gong, L., Guo, J., Tian, L., & Gao, Y. (2023) · Nature Biotechnology · doi:10.1038/s41587-023-01925-2 · Cited by 16
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“Therapeutic proteins encoded in messenger mRNA (mRNA) hold innumerable potential applications due to the modular nature and ability to provide customizable instructions to create functional proteins (1–3).”
BackgroundIonizable lipid nanoparticles for RAS protease delivery to inhibit cancer cell proliferation
Atsavapranee, E., Haley, R. M., Billingsley, M. M., Chan, A., Ruan, B., Figueroa‐Espada, C. G., Gong, N., Mukalel, A. J., Bryan, P. N., & Mitchell, M. J. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.05.015 · Cited by 16
Lipid nanoparticles-based RNA therapies for breast cancer treatment
Serpico, L., Zhu, Y., Maia, R. F., Sumedha, S., Shahbazi, M., & Santos, H. A. (2024) · Drug Delivery and Translational Research · doi:10.1007/s13346-024-01638-2 · Cited by 22
“The conclusion of their results showed that the pKa value should be higher than 5.4 to get efficient gene silencing [107].”
BackgroundInfluentialCationic HDL mimetics enhance in vivo delivery of self-replicating mRNA
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“Several non-viral replicon delivery methods have shown promise for vaccine development, including lipid nanoparticle formulations (LNPs) and cationic nanoemulsions (CNEs) (7, 10, 11).”
BackgroundTherapeutic Mechanism of Nucleic Acid Drugs
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Nanobiotechnology-Enabled mRNA Stabilization
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“PEGylated lipids), and cholesterol [1,44,81].”
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“LNPs are internalized by cells through the endocytosis mechanism and subsequently transferred to early endosomes, which further mature into late endosomes and eventually fuse with lysosomes to form endolysosomes, where degradation and digestion occur [7–9].”
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“As LNP technology continues to improve, applications are being sought requiring the delivery of longer transcripts, often longer than 10 kb, such as self-amplifying mRNA (sa-mRNA). sa-mRNA technology is a recent breakthrough for vaccine development 14 – 16 ; unlike conventional mRNA, sa-mRNA encodes information for no…”
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“Moreover, systemic administration of mRNA can trigger activation of innate immunity reminiscent of invading pathogens [6].”
BackgroundNew vector and vaccine platforms: mRNA, DNA, viral vectors
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“Both the 5’ and 3’untranslated regions (UTRs) contain critical regulatory elements [21,25,26] and can be derived from highly expressed human genes or use the pathogen’s original mRNA UTRs assuming optimization by natural evolution.”
BackgroundDelivery challenges for CRISPR—Cas9 genome editing for Duchenne muscular dystrophy
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Oncolytic Virus‐Like Nanoparticles for Tumor‐Specific Gene Delivery
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Golden Threads of Lipid Nanoparticles (LNPs) contributing to COVID-19 mRNA Vaccine: A Review
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“Consequently, engineering the sequences of these elements can lead to enhancements in in vivo translation [22].”
Synthetic nanomaterials for spleen-specific mRNA delivery
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One‐Component Ionizable Amphiphilic Janus Dendrimers for Targeted mRNA Delivery
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Metadata
- Authors
- Hajj, K. A., & Whitehead, K. A.
- Affiliations
- Carnegie Mellon University (US)
- Corresponding author
- Whitehead, Kathryn A.
- Venue
- Nature Reviews Materials
- Published
- 2017-09-12
- Volume
- 2
- Issue
- 10
- ISSN
- 2058-8437 (ISSN-L)
- OpenAlex
- W2754401101
- Cited by
- 799
- References
- 166
- Citations by year
- 2026: 61 · 2025: 122 · 2024: 110 · 2023: 126 · 2022: 124 · 2021: 101 · 2020: 82 · 2019: 40 · 2018: 32 · 2017: 1
- FWCI
- 3.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Reviews Materials (publishedVersion)
- Funders
- Defense Advanced Research Projects Agency (D16AP00143)
- Advanced Research Projects Agency
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- mRNA therapeutics, mRNA delivery, synthetic materials, lipid nanoparticles, mRNA vaccines, cancer immunotherapy, in vitro transcribed mRNA
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