Article
Chemistry, Multidisciplinary
Aviram Avital, Noy Sadot Muzika, Zohar Persky, Gili Bar, Yuval Michaeli, Yulia Fridman, Avishai Karny, Jeny Shklover, Janna Shainsky, Sigal Savaldi-Goldstein, Haim Weissman, Oded Shoseyov, Avi Schroeder
Summary: The study successfully utilized RNA interference (RNAi) technology to treat GLRaV-3 infection in Cabernet Sauvignon grapevines, effectively reducing viral titer and promoting recovery of the vines and grapes.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Oncology
Ji Young Yoo, Margaret Yeh, Balveen Kaur, Tae Jin Lee
Summary: Aberrant gene and miRNA expression can drive cancer development, and the modulation of these expressions provides a therapeutic opportunity. Recent advances in RNA nanotechnology offer potential for miRNA therapy, but the lack of a delivery platform remains a challenge.
Review
Pharmacology & Pharmacy
Kiara Fairman, Miao Li, Baitang Ning, Annie Lumen
Summary: PBPK modeling is a powerful tool with potential applications in the development of RNAi therapeutics, a class of drugs with unique pharmacokinetic properties. While there is active research in this area, there are still challenges to fully evaluating the utility of PBPK models for RNAi therapeutics. The current computational modeling approaches can support efficient development and approval of RNAi therapeutics, but further exploration and standardization are needed to optimize their use.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Nanoscience & Nanotechnology
Jordan Hartung, Nathan McCann, Erwin Doe, Hannah Hayth, Kheiria Benkato, M. Brittany Johnson, Mathias Viard, Kirill A. Afonin, Emil F. Khisamutdinov
Summary: Here, we present a toehold-mediated strand displacement strategy that enables the regulated shape-switching of nucleic acid nanoparticles (NANPs) from triangular to hexagonal architectures. The shape transitions were confirmed by various assays, and real-time monitoring was achieved using split-fluorogenic aptamers. Furthermore, the NANPs with embedded RNA aptamers demonstrated potential as drug delivery agents and biosensors, and a logic gate based on their shape-switching ability was constructed.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Chemistry, Multidisciplinary
Jinpeng Han, Yuchen Cui, Feng Li, Zi Gu, Dayong Yang
Summary: This study utilized natural polyphenol tannic acid (TA) to control the assembly and disassembly of nucleic acid nanocomplexes in cells for smart drug delivery and gene therapy. Through strong affinity between TA and nucleic acids/membrane proteins, the nanocomplex effectively targets cells and achieves spatiotemporally controllable disassembly within cells.
Review
Medicine, Research & Experimental
Peipei Wang, Yue Zhou, Arthur M. Richards
Summary: The comparison between siRNA and miRNA suggests that miRNA mimics have unique advantages due to their endogenous nature and the ability to regulate gene silencing effects, which will facilitate the development of miRNA mimic drugs.
Article
Biochemical Research Methods
Hao Liu, Fan Hong, Francesca Smith, John Goertz, Thomas Ouldridge, Molly M. Stevens, Hao Yan, Petr Sulc
Summary: Strand displacement is a widely used mechanism in nucleic acid nanotechnology, with toehold length, placement, and mismatches influencing reaction kinetics. Experimental studies show that longer toehold lengths and placement at the 5' end of the substrate accelerate the reaction, while mismatches closer to the toehold-duplex interface slow it down. The comparison of RNA and DNA displacement, as well as hybrid displacement, suggests a role of thermodynamic stabilities and helix rearrangements in the kinetics.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Elisabeth Houbron, Sophie Mockly, Sophia Rafasse, Nathalie Gros, Delphine Muriaux, Herve Seitz
Summary: RNA interference (RNAi) is widely used in research and has recently been approved for clinical applications. Developing siRNAs against SARS-CoV-2 could provide a basis for novel COVID-19 treatments and be adaptable to future variants or other viruses. By using computational tools and the latest mechanistic description of RNAi, we have designed siRNAs with high predicted activity and specificity. Our approach allows mismatches at tolerable positions and optimized siRNA duplex asymmetry, resulting in high antiviral activity against SARS-CoV-2 and excellent variant coverage.
Article
Biotechnology & Applied Microbiology
Qinghua Jiang, Shuzhen Yue, Kaixin Yu, Tian Tian, Jian Zhang, Huijun Chu, Zhumei Cui, Sai Bi
Summary: The study introduces an endogenous microRNA-activated DNA circuit for in situ generation of siRNAs, leading to enhanced gene silencing and anti-tumor effects.
JOURNAL OF NANOBIOTECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Chi-Ting Su, Daniel H. W. See, Jenq-Wen Huang
Summary: Kidney disease is a growing global burden, and the use of miRNAs and RNA therapy, which can be rapidly absorbed by kidneys, shows potential as an effective treatment option for renal diseases.
Review
Chemistry, Medicinal
Song Zhang, Zhujun Cheng, Yanan Wang, Tianyu Han
Summary: The progress of miRNA drugs in clinical trials is slow due to the characteristic of targeting multiple genes, leading to inevitable adverse effects.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Shi Chen, Li Xing, Douglas Zhang, Alba Monferrer, Thomas Hermann
Summary: This study reported a method for designing and preparing nano-sandwich composite materials through noncovalent assembly of protein, DNA, and RNA modules, successfully synthesizing the three-dimensional structure of a protein-RNA-DNA complex and providing a new design approach for bottom-up preparation of layered biomaterials.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Shi Chen, Li Xing, Douglas Zhang, Alba Monferrer, Thomas Hermann
Summary: This study reports the successful synthesis of a composite material composed of protein, DNA, and RNA through controlled self-assembly and precise positioning, with the 3D architecture confirmed through fluorescence labeling and cryo-electron microscopy studies. The synthesis strategy for the nano-sandwich composite provides a general blueprint for controlled noncovalent assembly of complex supramolecular architectures.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Pharmacology & Pharmacy
Mengnan Zhao, Rujing Wang, Kunmeng Yang, Yuhong Jiang, Yachen Peng, Yuke Li, Zhen Zhang, Jianxun Ding, Sanjun Shi
Summary: RNAs play crucial roles in disease progression and have become powerful targets for therapy and biomarkers for diagnosis. However, delivering therapeutic RNA efficiently to targeted locations and accurately detecting RNA markers remains challenging. Recent attention has focused on using nucleic acid nanoassemblies for diagnosis and treatment. Due to the flexibility and deformability of nucleic acids, these nanoassemblies can be fabricated into different shapes and structures. By hybridizing with other nucleic acids, such as DNA and RNA nanostructures, they can enhance RNA therapy and diagnostics. This review provides a brief overview of the construction and properties of nucleic acid nanoassemblies, their applications, and prospects for further development.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Biochemistry & Molecular Biology
Helen Bergquist, Raviteja Inturi, Rula Zain, Tanel Punga
Summary: RNA molecules can form specific RNA triplex structures, and the investigation on HAdV-4 VA RNAI suggests that it can potentially adopt a biologically relevant triplex structure, which plays a critical role in virus growth and development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Hyunsu Jeon, Yong Min Kim, Sangwoo Han, Hong Chul Moon, Jong Bum Lee
Summary: In this paper, innovative DNA-based gels and their applications in optoelectronics are proposed. The optoelectronic DNA-based gels, prepared through molecular complexation, demonstrate good mechanical characteristics and retain the electrochromic properties of DHV. Utilizing the moldability, voltage-tunable EC behavior, and biocompatibility/biodegradability of the gels, various functional electrochemical systems have been successfully demonstrated.
Review
Chemistry, Medicinal
Suji Kwon, Minseon Kwon, Seongeun Im, Kyuri Lee, Hyukjin Lee
Summary: Synthetic mRNA has emerged as a promising biotherapeutic agent, especially in the development of mRNA vaccines. It allows fast, scalable, and cost-effective production, and has shown unprecedented impact in the fight against the COVID-19 pandemic. This review summarizes the latest technology and the innate immunogenicity of in vitro transcribed (IVT) mRNA, and discusses its role in vaccine development and future directions.
ARCHIVES OF PHARMACAL RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Swarup Kumar Maji, Subin Yu, Eunshil Choi, Ju Won Lim, Dohyub Jang, Ga-young Kim, Sehoon Kim, Hyukjin Lee, Dong Ha Kim
Summary: In this study, a multifunctional nanohybrid material based on gold nanorods was developed for cancer diagnosis and treatment. The material exhibited stability and protective properties, enabling real-time near-infrared imaging and synergistic therapeutic effects.
Article
Chemistry, Multidisciplinary
Hee Jin, Michaela Jeong, Gyeongseok Lee, Minjeong Kim, Youngjo Yoo, Hyun Jin Kim, Jaeho Cho, Yun-Sil Lee, Hyukjin Lee
Summary: In this study, engineered lipid nanoparticles (LNPs) were developed for delivering RNA therapeutics to the lungs, showing potential as a new treatment regimen for pulmonary fibrosis.
ADVANCED FUNCTIONAL MATERIALS
(2023)
Article
Engineering, Environmental
Hyangsu Nam, Hyunsu Jeon, Hyejin Kim, Hong Yeol Yoon, Sun Hwa Kim, Jong Bum Lee
Summary: Researchers have developed a breathing therapeutic matrix using DNA microscaffold and modified cells, which can achieve therapeutic effects in vivo. The final construct has ultra-soft mechanical properties, allowing for treatment via injection without the need for surgery.
CHEMICAL ENGINEERING JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Alejandro J. Da Silva Sanchez, Kun Zhao, Sebastian G. Huayamares, Marine Z. C. Hatit, Melissa P. Lokugamage, David Loughrey, Curtis Dobrowolski, Shuaishuai Wang, Hyejin Kim, Kalina Paunovska, Yanina Kuzminich, James E. Dahlman
Summary: Lipid nanoparticles (LNPs) have been successfully used to deliver siRNA and mRNA drugs in humans, highlighting the potential impact of improving the therapeutic window of next-generation LNPs. By applying lessons from small-molecule chemistry, researchers have found that the stereochemistry of lipids within LNPs can influence mRNA delivery. In vivo experiments using 128 novel LNPs demonstrated that stereopure ionizable lipids deliver more mRNA compared to racemic and control LNPs, and are better tolerated.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Chemistry, Multidisciplinary
Afsane Radmand, Melissa P. Lokugamage, Hyejin Kim, Curtis Dobrowolski, Ryan Zenhausern, David Loughrey, Sebastian G. Huayamares, Marine Z. C. Hatit, Huanzhen Ni, Ada Del Cid, Alejandro J. Da Silva Sanchez, Kalina Paunovska, Elisa Schrader Echeverri, Aram Shajii, Hannah Peck, Philip J. Santangelo, James E. Dahlman
Summary: Lipid nanoparticles (LNPs) can deliver RNA to hepatocytes, highlighting their potential impact in non-liver delivery. By adding cationic helper lipids, researchers can redirect the LNPs to the lung; however, the biological response to these LNPs remains limited. This study examined the cellular response to different LNPs and found that the delivery of mRNA to the lung in vivo is influenced by cellular RNA and protein machinery.
Article
Chemistry, Multidisciplinary
Sebastian G. Huayamares, Melissa P. Lokugamage, Regina Rab, Alejandro J. Da Silva Sanchez, Hyejin Kim, Afsane Radmand, David Loughrey, Liming Lian, Yuning Hou, Bhagelu R. Achyut, Annette Ehrhardt, Jeong S. Hong, Cory D. Sago, Kalina Paunovska, Elisa Schrader Echeverri, Daryll Vanover, Philip J. Santangelo, Eric J. Sorscher, James E. Dahlman
Summary: Lipid nanoparticles are a clinically relevant way to deliver therapeutic mRNA to hepatocytes in patients. However, delivering LNP-mRNA to end-stage solid tumors such as head and neck squamous cell carcinoma remains challenging. This study uses a high-throughput LNP assay to evaluate the delivery of nucleic acids to HNSCC solid tumors in vivo using 94 chemically distinct nanoparticles.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Biotechnology & Applied Microbiology
Minjeong Kim, Michaela Jeong, Gyeongseok Lee, Yeji Lee, Jeongeun Park, Hyein Jung, Seongeun Im, Joo-Sung Yang, Kyungjin Kim, Hyukjin Lee
Summary: mRNA-based protein replacement therapy is a promising intervention for clinical disease treatment, but the immunogenicity of lipid nanoparticles (LNPs) has limited their translation to the clinic. In this study, a novel ionizable LNP with enhanced potency and safety was developed.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Review
Pharmacology & Pharmacy
Michaela Jeong, Yeji Lee, Jeongeun Park, Hyein Jung, Hyukjin Lee
Summary: RNA therapeutics have made significant breakthroughs in treating incurable diseases and genetic disorders by regulating gene expression. The development of COVID19 mRNA vaccines highlights the potential of RNA therapeutics in preventing infectious diseases and treating chronic diseases. However, efficient delivery of RNA into cells remains a challenge, and lipid nanoparticles (LNPs) are necessary for successful RNA therapeutics. This review focuses on the fundamental aspects of LNPs, their uses, recent advances, and breakthrough technologies to overcome limitations.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
Article
Multidisciplinary Sciences
Hyangsu Nam, Taehyeon Kim, Sunghyun Moon, Yoonbin Ji, Jong Bum Lee
Summary: Recent advances in CFPS have led to the development of a multimeric genomic DNA hydrogel (mGD-gel) that enhances protein yield. The mGD-gel, fabricated using RCCA with dual single-stranded circular plasmids, allows for easy manipulation of its shape and can be reused multiple times without affecting protein expression feasibility. This platform shows potential in CFPS systems for various biotechnological applications.
Article
Medicine, Research & Experimental
Jeong Pil Han, Yeji Lee, Jeong Hyeon Lee, Hye Yoon Chung, Geon Seong Lee, Yu Ri Nam, Myeongjin Choi, Kyoung-Sik Moon, Haeshin Lee, Hyukjin Lee, Su Cheong Yeom
Summary: Gene editing has been successfully used to develop an effective, safe, and sustainable treatment for hemophilia A. By targeting specific gene sites and using a combined rebalancing strategy, this method improves blood coagulation activity, reduces complications, and enhances survival in mice with hemophilia.
MOLECULAR THERAPY NUCLEIC ACIDS
(2023)
Review
Biochemistry & Molecular Biology
Yeji Lee, Michaela Jeong, Jeongeun Park, Hyein Jung, Hyukjin Lee
Summary: This article provides an overview of the immunological response to lipid nanoparticles and discusses the adverse effects and strategies for regulating the immunogenicity associated with these nanoparticles. Lipid nanoparticles have been utilized to enhance mRNA therapeutics and vaccines, but their recognition as foreign materials by the body leads to innate immune response, impacting adaptive immunity. Understanding the specific type of innate immune response triggered by lipid nanoparticles is crucial.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Chan-Jin Kim, Ga-Hyun Kim, Eun Hye Jeong, Hyukjin Lee, So-Jung Park
Summary: This study investigates how the nature of the hydrophobic core affects the molecular interactions of DNA block copolymer assemblies. Results show that DNA block copolymer micelles with different hydrophobic cores exhibit markedly different molecular and biological interactions, with DNA-b-PS displaying superior properties. The type of hydrophobic core polymer has a profound impact on the molecular and biological interactions of the DNA shell.
Article
Chemistry, Multidisciplinary
Hyunsu Jeon, Yong Min Kim, Sangwoo Han, Hong Chul Moon, Jong Bum Lee
Summary: In this study, innovative DNA-based gels were proposed and the optoelectronic DNA-based gels ((Op)DNA Gel) were prepared through molecular complexation, showing good mechanical characteristics and electrochromic properties. The gel demonstrated a promising platform for applications in various functional electrochemical systems.
