Article
Chemistry, Multidisciplinary
Jianbing Liu, Xuehe Lu, Tiantian Wu, Xiaohui Wu, Lin Han, Baoquan Ding
Summary: This study presents a novel strategy for constructing a nanoplatform that combines branched antisense DNA and siRNA for gene silencing. The multifunctional nucleic acid nanosystem efficiently inhibits tumor growth by targeting the tumor-associated gene PLK1 through combined gene silencing.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Pharmacology & Pharmacy
Veronique Noe, Eva Aubets, Alex J. Felix, Carlos J. Ciudad
Summary: PPRHs are DNA hairpins formed by intramolecular reverse Hoogsteen bonds that can bind to polypyrimidine stretches in dsDNA, leading to gene silencing, gene expression inhibition, point mutation correction, and applications as biosensor probes. They have high stability and lack immunogenicity, hepatotoxicity, or nephrotoxicity in vitro, making them a promising biotechnological tool with diverse biomedical applications.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Baoli Zhang, Xuehui Chen, Guoheng Tang, Ruofei Zhang, Jingyun Li, Guoming Sun, Xiyun Yan, Kelong Fan
Summary: In this study, a rationally designed nanocage-like protein carrier was developed for the effective delivery of TLR-activating nucleic acids. The carrier exhibited significantly improved delivery efficiency, achieving efficient cell uptake, specific lysosomal localization, and enhanced immune activation.
Article
Pharmacology & Pharmacy
Kazuto Yamazaki, Kenji Kubara, Yuta Suzuki, Taro Hihara, Daisuke Kurotaki, Tomohiko Tamura, Masashi Ito, Kappei Tsukahara
Summary: In this study, mannose-conjugated oligonucleotides were designed and used for targeted delivery to macrophages. The highly expressed mannose receptor in macrophages facilitated cellular uptake of the conjugated oligonucleotides. The delivery system showed efficient gene silencing in both human CD206-overexpressing cells and human macrophages, and demonstrated high distribution in the liver and pancreas after subcutaneous injection in mice.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2023)
Article
Chemistry, Multidisciplinary
Hassan H. Fakih, Adam Katolik, Elise Malek-Adamian, Johans J. Fakhoury, Sepideh Kaviani, Masad J. Damha, Hanadi F. Sleiman
Summary: Spherical nucleic acids (SNAs) show great potential as drug delivery vectors for nucleic acid therapeutics, with recent modifications enhancing stability and gene silencing potency. A cleavable DNA-based spacer is essential for maximum activity, and the modularity of FANA-SNA allows for versatile applications in gene silencing for various targets. Transfection-free delivery is superior for modified SNAs compared to free FANA oligonucleotides.
Article
Polymer Science
Pengfei Cui, Luping Ma, Pengju Jiang, Cheng Wang, Jianhao Wang
Summary: By gelating nucleic acid preparations with PEG, this study significantly improved the stability and transfection efficiency of nucleic acid preparations, contributing to the development of gene therapy drugs.
Review
Chemistry, Multidisciplinary
Agnieszka Tomaszewska-Antczak, Piotr Guga
Summary: This review summarizes the synthetic efforts on acyclic analogs of nucleic acids and evaluates their synthetic methods, thermal stability, and applications in biological and biochemical research as well as nanotechnology.
APPLIED SCIENCES-BASEL
(2021)
Article
Chemistry, Multidisciplinary
Fangjie Lyu, Takashi Tomita, Naoko Abe, Haruka Hiraoka, Fumitaka Hashiya, Yuko Nakashima, Shiryu Kajihara, Fumiaki Tomoike, Zhaoma Shu, Kazumitsu Onizuka, Yasuaki Kimura, Hiroshi Abe
Summary: This study describes the use of branched oligodeoxynucleotides (ODNs) with multiple reactive functional groups for topological mRNA capture. These fragmented ODNs efficiently formed topological complexes on template mRNA in vitro. In cell-based experiments targeting AcGFP mRNA, the bifurcated reactive ODNs showed a much larger gene silencing effect than the corresponding natural antisense ODN.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Fangjie Lyu, Takashi Tomita, Naoko Abe, Haruka Hiraoka, Fumitaka Hashiya, Yuko Nakashima, Shiryu Kajihara, Fumiaki Tomoike, Zhaoma Shu, Kazumitsu Onizuka, Yasuaki Kimura, Hiroshi Abe
Summary: This study describes the use of branched oligodeoxynucleotides (ODNs) with multiple reactive functional groups for topological mRNA capture. These fragmented ODNs efficiently formed topological complexes with template mRNA in vitro. In cell-based experiments targeting AcGFP mRNA, bifurcated reactive ODNs exhibited a stronger gene silencing effect compared to the corresponding natural antisense ODN. The topological capturing of mRNA by bifurcated reactive ODNs resulted in higher gene silencing effect than the corresponding canonical antisense strand.
CHEMICAL COMMUNICATIONS
(2023)
Review
Pharmacology & Pharmacy
Elias Fattal, Francois Fay
Summary: RNA therapeutics, including antisense oligonucleotides and small interfering RNAs, have shown success in clinical trials for inflammatory diseases by overcoming stability and cellular delivery challenges. However, there are still barriers to overcome in manufacturing and cellular/subcellular delivery for effective nucleic acid delivery to sites of inflammation other than the liver.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Article
Chemistry, Multidisciplinary
Yuto Honda, Sayaka Onodera, Hiroyasu Takemoto, Noor Faizah Che Harun, Takahiro Nomoto, Makoto Matsui, Keishiro Tomoda, Yudi Sun, Yutaka Miura, Nobuhiro Nishiyama
Summary: This study aims to develop a technology to control the activity of small interfering RNA (siRNA) in a thermo-responsive manner, even at temperatures close to body temperature. By conjugating siRNA with a thermally responsive copolymer, the activity of siRNA can be enhanced based on temperature changes. This technique offers a promising approach to selectively induce therapeutic effects of siRNA in vivo.
PHARMACEUTICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Minwook Shin, Io Long Chan, Yuming Cao, Alisha M. Gruntman, Jonathan Lee, Jacquelyn Sousa, Tomas C. Rodriguez, Dimas Echeverria, Gitali Devi, Alexandre J. Debacker, Michael P. Moazami, Pranathi Meda Krishnamurthy, Julia M. Rembetsy-Brown, Karen Kelly, Onur Yukselen, Elisa Donnard, Teagan J. Parsons, Anastasia Khvorova, Erik J. Sontheimer, Rene Maehr, Manuel Garber, Jonathan K. Watts
Summary: The study investigated the effectiveness of antisense oligonucleotides (ASOs) in different cell types of the lung using lineage markers, flow cytometry, and single-cell RNA sequencing. Fibroblasts were found to be the most susceptible to ASOs, with significant silencing also observed in endothelial cells.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Medicine, Research & Experimental
Mingju Shui, Zhejie Chen, Yi Chen, Qin Yuan, Hongyi Li, Chi Teng Vong, Mohamed A. Farag, Shengpeng Wang
Summary: Gene therapy, an effective medical intervention strategy, shows promising therapeutic effects in various diseases. However, the lack of safe and efficient drug carriers is a major drawback. Polyphenol-based carriers, due to their strong affinity to nucleic acids, are considered as promising anchors for gene delivery. This review summarizes the recent progress in polyphenol-assisted gene delivery and provides references for future vector design.
Article
Chemistry, Multidisciplinary
Melissa A. Pegues, Karol Szczepanek, Faruk Sheikh, Seth G. Thacker, Baikuntha Aryal, Mohamed K. Ghorab, Steven Wolfgang, Raymond P. Donnelly, Daniela Verthelyi, V. Ashutosh Rao
Summary: The fatty acid composition of polysorbate 80 may promote sub-visible particulate formation under stress conditions, but does not directly impact protein aggregation or biological activity.
PHARMACEUTICAL RESEARCH
(2021)
Review
Chemistry, Multidisciplinary
Fei Ding, Shuangye Zhang, Qian Chen, Hao Feng, Zhilei Ge, Xiaolei Zuo, Chunhai Fan, Qian Li, Qiang Xia
Summary: Programmable nucleic acid nanotechnology allows the customization of synthetic nucleic acid nanodevices with unprecedented precision, showing potential for precise immunoengineering.
Article
Biochemistry & Molecular Biology
Alexandra Maria Psaras, Simonas Valiuska, Veronique Noe, Carlos J. Ciudad, Tracy A. Brooks
Summary: In this study, three putative G4-forming sequences were identified within the KRAS gene, and oligonucleotides targeting these sequences were developed. These oligonucleotides were found to downregulate transcription of KRAS and inhibit cell proliferation, showing potential as novel therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biophysics
Adria Botet-Carreras, Manel Bosch Marimon, Ruben Millan-Solsona, Eva Aubets, Carlos J. Ciudad, Veronique Noe, M. Teresa Montero, Oscar Domenech, Jordi H. Borrell
Summary: This study assessed the ability of an engineered liposomal formulation to fuse and function as a nanocarrier in cells. Physicochemical changes on the cell surface and liposome-cell membrane interactions were observed using atomic force microscopy and confocal microscopy. The results confirmed the potential of the engineered liposomal formulation as a nanocarrier.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2023)
Article
Chemistry, Organic
Laura G. Rodriguez, Ana Delgado, Carlos J. Ciudad, Veronique Noe, Josep Bonjoch, Ben Bradshaw
Summary: A two-step reaction was developed to synthesize a ring system found in natural products. The reaction was explored with eight substituted nitrobenzenes, achieving yields of up to 87%. One of the benzazocine compounds, 4h, exhibited high cytotoxicity and was active against eight cancer cell lines.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Ana Delgado, Rosa Griera, Nuria Llor, Ester Lopez-Aguilar, Maria Antonia Busquets, Veronique Noe, Carlos J. J. Ciudad
Summary: The article describes the synthesis and characterization of a compound called TROPY, which can efficiently deliver oligonucleotides and plasmid DNA into mammalian cells. The experiments show that TROPY can reduce cell viability, increase apoptosis, and decrease survivin mRNA and protein levels in human cancer cells.
Article
Biochemistry & Molecular Biology
Ester Lopez-Aguilar, Patricia Fernandez-Nogueira, Gemma Fuster, Neus Carbo, Carlos J. Ciudad, Veronique Noe
Summary: Therapeutic oligonucleotides targeting the overexpressed ERBB2 gene in positive HER-2 breast tumors showed inhibitory effects in cell viability, mRNA and protein levels. Combination with trastuzumab enhanced the therapeutic effects in vitro and reduced tumor growth in vivo. These findings provide preclinical evidence for the potential use of PPRHs as a therapeutic tool for breast cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Simonas Valiuska, Alexandra Maria Psaras, Veronique Noe, Tracy A. Brooks, Carlos J. Ciudad
Summary: The oncogene MYC plays multiple key roles in cancer, and targeting its expression or function is a promising therapeutic strategy. In this study, Polypurine Reverse Hoogsteen hairpins (PPRHs) were used to target GC-rich regions, including a G-quadruplex-forming region, in the MYC promoter and intronic regions. Two lead PPRHs were found to have high potential for further development as a novel approach for stabilizing the G4 structure and modulating MYC expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Oncology
Alexandra Maria Psaras, Simonas Valiuska, Veronique Noe, Carlos J. Ciudad, Tracy A. Brooks
Article
Biochemistry & Molecular Biology
Anna Avino, Carlos Cuestas-Ayllon, Manuel Gutierrez-Capitan, Lluisa Vilaplana, Valeria Grazu, Veronique Noe, Eva Balada, Antonio Baldi, Alex J. Felix, Eva Aubets, Simonas Valiuska, Arnau Dominguez, Raimundo Gargallo, Ramon Eritja, M-Pilar Marco, Cesar Fernandez-Sanchez, Jesus Martinez de la Fuente, Carlos J. Ciudad
Summary: An innovative analytical approach based on sandwich oligonucleotide hybridization has been developed, which can be adapted to multiple biosensing devices for the rapid detection of pathogens.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
David Tamborero, Rodrigo Dienstmann, Maan Haj Rachid, Jorrit Boekel, Adria Lopez-Fernandez, Markus Jonsson, Ali Razzak, Irene Brana, Luigi De Petris, Jeffrey Yachnin, Richard D. Baird, Yohann Loriot, Christophe Massard, Patricia Martin-Romano, Frans Opdam, Richard F. Schlenk, Claudio Vernieri, Michele Masucci, Xenia Villalobos, Elena Chavarria, Judith Balmana, Giovanni Apolone, Carlos Caldas, Jonas Bergh, Ingemar Ernberg, Stefan Frohling, Elena Garralda, Claes Karlsson, Josep Tabernero, Emile Voest, Jordi Rodon, Janne Lehtio
Summary: This article presents the implementation of the Molecular Tumor Board Portal, a system that integrates and interprets genomics and clinical data to support clinical decision-making in precision oncology. The system automates the interpretation and reporting of sequencing results, reducing errors and promoting consistent decision-making and data capture. It also facilitates collaborative discussion through information-rich patient reports and interactive content.