Review
Pharmacology & Pharmacy
Chisato Terada, Seiya Kawamoto, Asako Yamayoshi, Tsuyoshi Yamamoto
Summary: Oligonucleotide therapeutics have made significant progress in the treatment of diseases, but are still limited by side effects. This review aims to explore avenues for symbiotic engineering of oligonucleotide therapeutics through the discussion of physicochemical characteristics, in order to achieve more effective and safer drugs.
Article
Chemistry, Multidisciplinary
Carme Fabrega, Anna Avino, Ramon Eritja
Summary: The article discusses the advancements in the therapeutic and diagnostic applications of nucleic acids over the past decade, including studies on siRNA modifications, novel conjugate designs, and the use of nanostructures for drug delivery. These interdisciplinary research efforts have expanded the applications of nucleic acids in various fields.
Review
Pharmacology & Pharmacy
Carme Fabrega, Anna Avino, Natalia Navarro, Andreia F. Jorge, Santiago Grijalvo, Ramon Eritja
Summary: In this study, the conjugation of oligonucleotides with lipids and peptides for the development of therapeutics with improved pharmacokinetics is reviewed.
Review
Chemistry, Organic
Christopher Liczner, Kieran Duke, Gabrielle Juneau, Martin Egli, Christopher J. Wilds
Summary: Over the past 25 years, there has been significant acceleration in the development of oligonucleotide-based therapeutics, leading to the market approval of many new drugs for treating various diseases. Chemically modified oligonucleotides with interesting biophysical properties that can bind to targets and be tolerated by cellular machinery have been explored for gene silencing.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Hartmut Jahns, Rohan Degaonkar, Peter Podbevsek, Swati Gupta, Anna Bisbe, Krishna Aluri, John Szeto, Pawan Kumar, Sarah LeBlanc, Tim Racie, Christopher R. Brown, Adam Castoreno, Dale C. Guenther, Vasant Jadhav, Martin A. Maier, Janez Plavec, Martin Egli, Muthiah Manoharan, Ivan Zlatev
Summary: In this study, small circular interfering RNAs (sciRNAs) were synthesized and evaluated for their therapeutic potential. Circularization improved metabolic stability of the sense strand and eliminated off-target effects, resulting in potent GaINAc-sciRNAs at therapeutically relevant doses. Physicochemical studies and NMR-based structural analysis shed light on the interactions of this novel class of siRNAs with the RNAi machinery.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Hiroki Tanaka, Nae Takata, Yu Sakurai, Tokuyuki Yoshida, Takao Inoue, Shinya Tamagawa, Yuta Nakai, Kota Tange, Hiroki Yoshioka, Masatoshi Maeki, Manabu Tokeshi, Hidetaka Akita
Summary: This study investigated the optimal lipid composition of LNPs for the delivery of siRNA and ASO, finding that the optimal compositions for siRNA and ASO were different and differed from those reported for mRNA in previous studies. The key processes for successful delivery of mRNA, siRNA, and ASO were identified as extracellular stability, endosomal escape, and cellular uptake, respectively, indicating the importance of optimizing LNP lipid compositions based on the type of nucleic acids being delivered.
Review
Pharmacology & Pharmacy
Yannis Dimitroglou, Constantina Aggeli, Panagiotis Theofilis, Panagiotis Tsioufis, Evangelos Oikonomou, Konstantinos Tsioufis, Dimitris Tousoulis
Summary: Coronary artery disease (CAD) is the leading cause of morbidity and mortality in Western societies, and novel biomarkers, including Lp(a), are being explored as potential diagnostic and therapeutic targets to improve outcomes. Several studies have associated high Lp(a) levels with increased risk for acute coronary syndromes (ACS), and specific treatment options targeting Lp(a) have become available. This review aims to present the current evidence regarding the use of Lp(a) as a biomarker for predicting increased CAD risk and discuss the future prospects of pharmaceutical reduction of Lp(a) as a therapeutic target in high-risk patients.
CURRENT PHARMACEUTICAL DESIGN
(2023)
Review
Biochemistry & Molecular Biology
Haoyu Xiong, Rakesh N. Veedu, Sarah D. Diermeier
Summary: Oligonucleotide therapeutics show promising clinical outcomes in diseases such as Duchenne muscular dystrophy, familial amyloid neuropathies, and macular degeneration. Although no approved oligonucleotide drug exists for any type of cancer, results from preclinical studies and clinical trials are encouraging.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Alina T. He, Jinglei Liu, Feiya Li, Burton B. Yang
Summary: Significant progress has been made in circular RNA (circRNA) research in recent years. CircRNAs are considered potential therapeutic targets and can be manipulated through various strategies for gain-of-function or loss-of-function. Although still in the early stages, the CRISPR/Cas13 system shows promise in efficiently knocking down circRNAs.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Multidisciplinary Sciences
Chi Zhu, Justin Y. Lee, Jia Z. Woo, Lei Xu, Xammy Nguyenla, Livia H. Yamashiro, Fei Ji, Scott B. Biering, Erik Van Dis, Federico Gonzalez, Douglas Fox, Eddie Wehri, Arjun Rustagi, Benjamin A. Pinsky, Julia Schaletzky, Catherine A. Blish, Charles Chiu, Eva Harris, Ruslan I. Sadreyev, Sarah Stanley, Sakari Kauppinen, Silvi Rouskin, Anders M. Naar
Summary: A novel therapeutic strategy using locked nucleic acid antisense oligonucleotides (LNA ASOs) has been developed to target SARS-CoV-2 RNA. It disrupts viral replication with high efficacy and has shown promising results in both in vitro and in vivo experiments, including COVID-19 mouse models. This approach could potentially complement current vaccination efforts and help reduce transmission and severity of COVID-19.
NATURE COMMUNICATIONS
(2022)
Review
Spectroscopy
Soheil Pourshahian
Summary: This article discusses the synthesis, impurities, and degradation products of oligonucleotides, as well as the application of liquid chromatography combined with mass spectrometry in the characterization and quantification of these substances. It also examines methods for determining oligonucleotide sequences through gas-phase fragmentation and indirect mass spectrometric methods.
MASS SPECTROMETRY REVIEWS
(2021)
Review
Oncology
Kurt Sartorius, Samuel O. Antwi, Anil Chuturgoon, Lewis R. Roberts, Anna Kramvis
Summary: This review paper investigates the potential of RNA interference (RNAi) as a therapeutic option for HCC and explores various RNAi technologies. It outlines three primary strategies of RNAi interventions and discusses challenges such as chemical and delivery problems, targeting issues, and immune reactions.
FRONTIERS IN ONCOLOGY
(2022)
Review
Oncology
Veronica Gomez-Gil
Summary: While the importance of TGF beta in cancer development has long been recognized, a successful therapy targeting this cytokine has not been developed yet. Various strategies are being tested to regulate TGF beta expression in cancer treatment, but the dual role of TGF beta and its crosstalk with other signaling pathways may compromise treatment effectiveness.
Review
Pharmacology & Pharmacy
D. Collotta, I. Bertocchi, E. Chiapello, M. Collino
Summary: Antisense oligonucleotides (ASOs) are short synthetic RNA or DNA molecules that can directly regulate disease-causing genes. They are an emerging class of drugs for treating orphan genetic disorders. Constant technological advances are crucial in overcoming limitations in pharmacology, toxicology, and formulation to translate ASOs into successful clinical applications.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Keisuke Koyasu, Akash Chandela, Yoshihito Ueno
Summary: A novel method of non-terminal conjugation of spermine into the passenger strand of siRNA was synthesized and evaluated. The conjugation at non-terminal positions resulted in increased stability and resistance against nucleases, but showed reduced gene-silencing activity.
