Since the discovery of classical B-DNA in the early 1960s, discussion has been initiated about the existence of alternative nucleic acid structures in the genome. The non-canonical nucleic acid secondary structures occur spontaneously in the repeat sequences that are common, especially in disease-related genes. The properties of nucleic acids to adopt secondary structures such as hairpins, triplexes, quadruplexes, and i-motifs, etc., can control basic cellular processes, and thus altered levels of gene expression are associated with many human genetic diseases including cancer and neurological disorders. For example, abnormally expanded DNA and RNA repeat sequences usually form various hairpins or cruciform structures that often become pathogenic and lead to many incurable neurological diseases. In addition, non-canonical structures are often associated with DNA damage and genomic instabilities, which are common mechanisms for certain cancers. To be precise, secondary nucleic acid structures are as important as their sequences in regulating their cellular functions and controlling disease outcomes. Therefore, these structures have emerged as potential therapeutic targets for various genetic diseases.
Recent advances in technology made it possible to study functional roles based on the actual formation of a particular structure. Using high-throughput genomics and computational approaches, it is possible to identify the potential non-canonical sites of secondary structure formation in the genome. Structural technologies have allowed us to develop new methods by targeting secondary nucleic acid structures to control cellular processes. Moreover, the dynamic nature of nucleic acids to adopt secondary structures makes them a promising building material for constructing tools such as synthetic switches to solve problems in human diseases and medicine. In this Research Topic, we aim to cover a broader perspective of current advances in understanding the structural and functional roles of DNA, RNA and DNA/RNA non-canonical disease-associated structures, novel approaches to detect their existence in human cells, therapeutic interventions to control the roles of non-canonical nucleic acids in cells, and the development of synthetic functional nucleic acid tools to solve problems related to genetic diseases. Thus, the main objective of this topic is to target studies that broadly fall into the derivation of novel roles of non-canonical nucleic acids for facilitating their implementation in the treatment of human genetic diseases.
We welcome the Original Research articles, Reviews, Mini-reviews, and Perspective articles. Themes of interest include, but are not limited to:
• Structural and/or functional studies of disease-relevant DNA/RNA secondary structures (duplexes, hairpins, triplexes, i-motif, quadruplexes, etc.).
• Identification and characterization of novel non-canonical nucleic acid structures and their association with interacting molecules involved in human diseases.
• Studies on the conformations, dynamics and mechanisms of nucleotide repeat expansions associated with neurological diseases.
• Computational studies to predict non-canonical structural formations in genomic regions with the experimental evaluations relevant to human genetic diseases.
• Studies dealing with the new methods or techniques for evaluating the role of disease-associated non-canonical nucleic acids in the genome.
• Targeting of non-canonical nucleic acid secondary structures with small molecules for the development of innovative therapeutic strategies against cancers and neurological diseases.
• Studies related to the development of new functional non-canonical nucleic acid structures for applications in the diagnosis and therapy of human diseases.
The Topic Editors acknowledge Dr Roshan Satange (National Chung Hsing University) who has acted as coordinator. Dr. Satange has contributed to the preparation of the proposal for this Research Topic.
