☆ 4.7 Review

Nanobiotechnology-Enabled mRNA Stabilization

PHARMACEUTICS (2023)

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Correction Biotechnology & Applied Microbiology

Engineering circular RNA for enhanced protein production (Jul, 10.1038/s41587-022-01393-0, 2022)

Robert Chen et al.

NATURE BIOTECHNOLOGY (2023)

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Article Chemistry, Multidisciplinary

Stabilizing RNA Nanovaccines with Transformable Hyaluronan Dynamic Hydrogel for Durable Cancer Immunotherapy

Fuhao Jia et al.

Summary: This study introduces a method of using hyaluronan dynamic hydrogel to stabilize lipid nanoparticles and protect mRNA, enabling efficient delivery of tumor antigen encoding mRNA to dendritic cells and subsequent antigen-specific CD8(+) T cell-mediated tumor cell killing.

ADVANCED FUNCTIONAL MATERIALS (2023)

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Article Biotechnology & Applied Microbiology

Lyophilization provides long-term stability for a lipid nanoparticle-formulated , nucleoside-modified mRNA vaccine

Hiromi Muramatsu et al.

Summary: Research demonstrates that nucleoside-modified mRNA-LNP vaccines can be lyophilized and maintain their physicochemical properties after storage at room temperature for 12 weeks or at 4℃ for at least 24 weeks. Comparative studies also show that lyophilized mRNA-LNP vaccines maintain high expression and immunogenicity even after storage.

MOLECULAR THERAPY (2022)

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Review Cell Biology

Roles of mRNA poly(A) tails in regulation of eukaryotic gene expression

Lori A. Passmore et al.

Summary: Recent studies have shown that poly(A) tails play a complex role in the cytoplasm, including promoting translation and controlling mRNA stability through deadenylation. The length of poly(A) tails is correlated with translation rate and mRNA lifespan, indicating a significant role in gene regulation.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2022)

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Article Biochemistry & Molecular Biology

Determinants of the temperature adaptation of mRNA degradation

Vincent Jaquet et al.

Summary: The rate of chemical reactions increases with temperature, but biochemical reactions can deviate from this relationship. The degradation of mRNAs is influenced by translation and codon composition. A method was developed to identify a neutral half-life for mRNA stabilization through translation. Some codons and Upf1 compensate for temperature in mRNA degradation.

NUCLEIC ACIDS RESEARCH (2022)

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Article Engineering, Biomedical

Bridging mRNA and Polycation Using RNA Oligonucleotide Derivatives Improves the Robustness of Polyplex Micelles for Efficient mRNA Delivery

Naoto Yoshinaga et al.

Summary: The study successfully stabilized Polyplex micelles (PMs) by developing RNA oligonucleotide (OligoRNA) derivatives to bridge mRNA and polycation, improving their stability against polyion exchange reaction and ribonuclease attack. This bridging strategy provides a new approach for mRNA delivery by enhancing the efficiency of mRNA introduction in cultured cells and mouse lungs after intratracheal administration.

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Review Materials Science, Biomaterials

Non-viral delivery of the CRISPR/Cas system: DNA versus RNA versus RNP

Yi Lin et al.

Summary: The CRISPR/Cas technology has become an essential tool in biomedical research, offering hope for therapeutic applications in genomic DNA modification. Delivery strategies for CRISPR/Cas components include plasmid DNA, RNA, and Cas9 ribonucleoproteins. RNA-based delivery has shown promising results in clinical trials, while the translation of ribonucleoprotein delivery to systemic genome editing in patients has not been achieved yet.

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Protein-Encoding Free-Standing RNA Hydrogel for Sub-Compartmentalized Translation

So Yeon Ahn et al.

Summary: In this research, a stable RNA hydrogel was developed through a sequential process, which can exhibit catalytic activity and enhance protein expression in specific translation environments.

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Effective mRNA Protection by Poly(l-ornithine) Synergizes with Endosomal Escape Functionality of a Charge-Conversion Polymer toward Maximizing mRNA Introduction Efficiency

Anjaneyulu Dirisala et al.

Summary: This study integrates the protective effect against nucleases and the endosomal escape capability into a single polyplex by fine-tuning the catiomer chemical structure and incorporating the endosomal escape modality for efficient mRNA delivery. The methylene spacer length on the catiomer side chain significantly affects the nuclease stability of the polyplex, and introducing a charge-conversion polymer can improve endosomal escape efficiency by approximately 80-fold in cultured cells. The system synergizes PLO's protective effect against nucleases and CCP's endosomal escape capability, leading to enhanced protein expression efficiency from mRNA delivery.

MACROMOLECULAR RAPID COMMUNICATIONS (2022)

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Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics

Kathrin Leppek et al.

Summary: The authors developed a platform called PERSIST-seq for studying mRNA stability, ribosome load, and solution stability to improve mRNA therapeutics. They found that in-cell stability is a greater driver of protein output than ribosome load and introduced a method called In-line-seq for mitigating hydrolytic degradation. Their findings demonstrate the simultaneous improvement of mRNA stability and protein expression.

NATURE COMMUNICATIONS (2022)

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Article Materials Science, Multidisciplinary

Targeting strategies for mRNA delivery

Randall A. Meyer et al.

Summary: mRNA gene therapy has the potential to enable various therapeutic applications, but its successful clinical translation has been limited due to inadequate understanding of organ-specific protein expression. Studies have shown that carrier material properties and routes of administration are important factors in mRNA therapeutic expression profiles. Understanding trends in tissue-specific mRNA delivery materials can unlock the full potential of therapeutic mRNA medicines.

MATERIALS TODAY ADVANCES (2022)

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Article Engineering, Biomedical

An imidazole modified lipid confers enhanced mRNA-LNP stability and strong immunization properties in mice and non-human primates

Manon Ripoll et al.

Summary: mRNA vaccine technology has great potential in fighting infectious diseases, as shown by the licensing of Comirnaty (R) (Pfizer/BioNtech) and Spikevax (R) (Moderna), two mRNA-based vaccines, during the Covid-19 crisis. However, current mRNA/LNP vaccine technology has limitations, including thermostability. A novel imidazole modified lipid, DOGIM4, combined with standard helper lipids, can improve the thermostability of mRNA/LNP.

BIOMATERIALS (2022)

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Article Chemistry, Multidisciplinary

Polypyrrole Nanoenzymes as Tumor Microenvironment Modulators to Reprogram Macrophage and Potentiate Immunotherapy

Weiwei Zeng et al.

Summary: In this study, a copper-doped polypyrrole nanozyme was developed to cause irreversible oxidative stress damage and reverse the redox balance in the tumor microenvironment. The modified nanozyme could reverse the immunosuppressive tumor microenvironment and inhibit tumor growth.

ADVANCED SCIENCE (2022)

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Review Biochemistry & Molecular Biology

The Role of Cryoprotective Agents in Liposome Stabilization and Preservation

George Frimpong Boafo et al.

Summary: This review discusses the use of cryoprotectants to improve the stability of liposomes as drug delivery vehicles. Studies have shown that increasing the concentration of cryoprotectants improves liposomal stability and reduces aggregation. Different types of cryoprotectants have distinct effective mechanisms, and the combination of multiple cryoprotectants may have synergistic effects.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Injectable Immunotherapeutic Hydrogel Containing RNA-Loaded Lipid Nanoparticles Reshapes Tumor Microenvironment for Pancreatic Cancer Therapy

Chao Gao et al.

Summary: In this study, a novel hydrogel was developed for pancreatic cancer immunotherapy. The hydrogel can reshape the tumor microenvironment, increase the number of M1 phenotype macrophages, and control tumor growth.

NANO LETTERS (2022)

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The roles of polymers in mRNA delivery

Pei Huang et al.

Summary: This review summarizes the development of polymeric nanocarriers for mRNA delivery and discusses approaches to enhance mRNA transfection efficiency. The authors propose conclusions and perspectives on the clinical translation of mRNA therapy, believing that the introduction of mRNA will lead to promising techniques for disease prevention and treatment in the future.

MATTER (2022)

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Review Chemistry, Multidisciplinary

Emerging mRNA technologies: delivery strategies and biomedical applications

Yufen Xiao et al.

Summary: This article provides an overview of the significant advancements in emerging mRNA technologies, along with the accompanying chemical designs and principles. Various nanoparticle delivery strategies are discussed, and typical mRNA delivery platforms for various biomedical applications are highlighted. The article also offers insights into the challenges and future development of clinical translation for these mRNA technologies.

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Addressing the Cold Reality of mRNA Vaccine Stability

Daan J. A. Crommelin et al.

Summary: This commentary discusses the challenges surrounding the stability and formulation of mRNA vaccines, highlighting the need to optimize their formulation for enhanced stability during storage, transport, and administration. Additionally, the mRNA vaccine approach shows evidence of human immunogenicity against multiple viral pathogens and the ability to rapidly adapt to emerging infectious diseases.

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Next-Generation Vaccines: Nanoparticle-Mediated DNA and mRNA Delivery

William Ho et al.

Summary: Nucleic acid vaccines hold promise as an immunization method for combating pandemics, with nanoparticles being a top candidate for successful DNA/mRNA vaccine delivery due to their unique properties.

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Zwitterionic Phospholipidation of Cationic Polymers Facilitates Systemic mRNA Delivery to Spleen and Lymph Nodes

Shuai Liu et al.

Summary: The study introduces a rational design and combinatorial synthesis of zwitterionic phospholipidated polymers (ZPPs) for efficient mRNA delivery to spleen and lymph nodes, with potential for substantial immunotherapeutic applications.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2021)

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mRNA loading into ATP-responsive polyplex micelles with optimal density of phenylboronate ester crosslinking to balance robustness in the biological milieu and intracellular translational efficiency

Naoto Yoshinaga et al.

Summary: A novel carrier design was introduced to protect and release mRNA in the cytosol for efficient protein expression, balancing stability in the biological milieu and ATP-responsive release through the modulation of structural factors. Furthermore, the optimal formulation was enhanced by incorporating cholesterol moieties for prolonged blood circulation post intravenous injection.

JOURNAL OF CONTROLLED RELEASE (2021)

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In Situ Transforming RNA Nanovaccines from Polyethylenimine Functionalized Graphene Oxide Hydrogel for Durable Cancer Immunotherapy

Yue Yin et al.

Summary: The research team developed a transformable hydrogel that can generate nanovaccines for up to 30 days after injection, showing promising potential for effective cancer immunotherapy.

NANO LETTERS (2021)

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PEGylation of poly(amine-co-ester) polyplexes for tunable gene delivery

Molly K. Grun et al.

Summary: The study found that low concentrations of PACE-PEG can improve polyplex stability but also inhibit transfection efficiency. In vivo, the effect of PACE-PEG incorporation on transfection varied by delivery route, and excess PEGylation was detrimental to vehicle function.

BIOMATERIALS (2021)

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Review Pharmacology & Pharmacy

mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability

Linde Schoenmaker et al.

Summary: The current mRNA-lipid nanoparticle COVID-19 vaccines require storage at low temperatures due to instability. Improving mRNA nucleotide composition, understanding the impact of mRNA environment within LNPs, and exploring drying techniques can enhance vaccine stability.

INTERNATIONAL JOURNAL OF PHARMACEUTICS (2021)

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Review Cell Biology

The Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines

Pedro Morais et al.

Summary: The current COVID-19 pandemic has led to widespread disruption globally, prompting the rapid development of COVID-19 vaccines, with mRNA-based vaccines showing high efficacy. The presence of N1-methyl-pseudouridine modification in mRNA has been identified as an important factor in the effectiveness of the vaccines.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Review Chemistry, Multidisciplinary

Lipid Nanoparticles-From Liposomes to mRNA Vaccine Delivery, a Landscape of Research Diversity and Advancement

Rumiana Tenchov et al.

Summary: Lipid nanoparticles (LNPs) have become promising vehicles in the pharmaceutical industry for delivering various therapeutics, particularly highlighted in the COVID-19 mRNA vaccines. LNPs exhibit versatility and physical stability, allowing for targeted delivery of therapeutic drugs to specific locations within the body. Liposomes, an early version of LNPs, have already been widely applied in medical practice.

ACS NANO (2021)

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Article Chemistry, Multidisciplinary

One-Component Multifunctional Sequence-Defined Ionizable Amphiphilic Janus Dendrimer Delivery Systems for mRNA

Dapeng Zhang et al.

Summary: Efficient delivery of nucleic acids is crucial for genetic nanomedicine. While viral vectors are highly efficient, they can also cause severe immune responses, toxicity, and mutations. Nonviral lipid nanoparticles containing specific components show promise for mRNA delivery, but challenges such as stability at low temperatures need to be addressed.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2021)

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Review Biotechnology & Applied Microbiology

mRNA vaccines for infectious diseases: principles, delivery and clinical translation

Namit Chaudhary et al.

Summary: mRNA vaccines have been established as a rapid, effective, and safe approach for protecting individuals from infectious diseases, especially during the COVID-19 pandemic. Further research is needed to optimize mRNA vaccine design, delivery, and applications for a range of infectious diseases.

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Theoretical basis for stabilizing messenger RNA through secondary structure design

Hannah K. Wayment-Steele et al.

Summary: RNA hydrolysis poses challenges for mRNA-based vaccines and therapeutics due to issues in manufacturing, long-term storage, global delivery, and in vivo stability. Redesigning RNAs to form double-stranded regions could reduce hydrolysis, with algorithms like those on the Eterna platform showing promise in creating 'superfolder' mRNAs with increased stability and diverse features beneficial for translation and immunogenicity. Ongoing research aims to maximize mRNA stability and longevity through innovative design strategies and computational approaches.

NUCLEIC ACIDS RESEARCH (2021)

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Review Nanoscience & Nanotechnology

Lipid nanoparticles for mRNA delivery

Xucheng Hou et al.

Summary: Lipid nanoparticle-mRNA formulations have successfully entered clinical use as COVID-19 vaccines, representing a major milestone in mRNA therapeutics. This review discusses the design of lipid nanoparticles for mRNA delivery, emphasizing key points for clinical translation and preclinical studies of lipid nanoparticle-mRNA therapeutics for various diseases.

NATURE REVIEWS MATERIALS (2021)

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Review Immunology

Challenges of Storage and Stability of mRNA-Based COVID-19 Vaccines

Mohammad N. Uddin et al.

Summary: In response to the emergence of COVID-19, mRNA-based vaccines by Moderna and BioNTech/Pfizer have been identified as the most effective ones. However, the global use of these vaccines is limited by ultracold storage requirements. Therefore, finding strategies to increase stability of mRNA-based vaccines in relatively higher temperatures is crucial to address the current global pandemic and upcoming new waves.

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Optimization of lipid nanoparticles for the delivery of nebulized therapeutic mRNA to the lungs

Melissa P. Lokugamage et al.

Summary: This study optimized the design of lipid nanoparticles for the efficient delivery of therapeutic mRNA to the lungs via nebulization, resulting in protection of mice from a lethal challenge of H1N1 influenza A virus and more efficient delivery of mRNA compared to LNPs previously optimized for systemic delivery. The cluster approach to LNP design may facilitate the optimization of LNPs for other administration routes and therapeutics.

NATURE BIOMEDICAL ENGINEERING (2021)

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Emerging Concepts of Nanobiotechnology in mRNA Delivery

Yue Wang et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2020)

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The emerging role of RNA modifications in the regulation of mRNA stability

Sung Ho Boo et al.

EXPERIMENTAL AND MOLECULAR MEDICINE (2020)

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A Multi-Targeting, Nucleoside-Modified mRNA Influenza Virus Vaccine Provides Broad Protection in Mice

Alec W. Freyn et al.

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Ribosome Collisions Trigger General Stress Responses to Regulate Cell Fate

Colin Chih-Chien Wu et al.

CELL (2020)

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Ribosome collisions trigger cis-acting feedback inhibition of translation initiation

Szymon Juszkiewicz et al.

ELIFE (2020)

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Long-term storage of lipid-like nanoparticles for mRNA delivery

Pengxuan Zhao et al.

BIOACTIVE MATERIALS (2020)

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Nanoparticles containing constrained phospholipids deliver mRNA to liver immune cells in vivo without targeting ligands

Zubao Gan et al.

BIOENGINEERING & TRANSLATIONAL MEDICINE (2020)

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Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery

Piotr S. Kowalski et al.

MOLECULAR THERAPY (2019)

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Oligo(serine ester) Charge-Altering Releasable Transporters: Organocatalytic Ring-Opening Polymerization and their Use for in Vitro and in Vivo mRNA Delivery

Nancy L. Benner et al.

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Translation affects mRNA stability in a codon-dependent manner in human cells

Qiushuang Wu et al.

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Bundling mRNA Strands to Prepare Nano-Assemblies with Enhanced Stability Towards RNase for In Vivo Delivery

Naoto Yoshinaga et al.

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A lipid-encapsulated mRNA encoding a potently neutralizing human monoclonal antibody protects against chikungunya infection

Nurgun Kose et al.

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Asha Kumari Patel et al.

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Nanoparticles Containing Oxidized Cholesterol Deliver mRNA to the Liver Microenvironment at Clinically Relevant Doses

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Norbert Pardi et al.

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Jacob A. Poliskey et al.

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PECAM-1 directed re-targeting of exogenous mRNA providing two orders of magnitude enhancement of vascular delivery and expression in lungs independent of apolipoprotein E-mediated uptake

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Control of phosphorothioate stereochemistry substantially increases the efficacy of antisense oligonucleotides

Naoki Iwamoto et al.

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Khalid A. Hajj et al.

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Zwitterionic Nanocarrier Surface Chemistry Improves siRNA Tumor Delivery and Silencing Activity Relative to Polyethylene Glycol

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Circular RNAs are long-lived and display only minimal early alterations in response to a growth factor

Yehoshua Enuka et al.

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Polymer-Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs

James C. Kaczmarek et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2016)

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Progress in the development of lipopolyplexes as efficient non-viral gene delivery systems

Mehdi Rezaee et al.

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Lena M. Kranz et al.

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