Nucleic Acids and Their Analogues for Biomedical Applications

Abstract

Nucleic acids are emerging as powerful and functional biomaterials due to their molecular recognition ability, programmability, and ease of synthesis and chemical modification. Various types of nucleic acids have been used as gene regulation tools or therapeutic agents for the treatment of human diseases with genetic disorders. Nucleic acids can also be used to develop sensing platforms for detecting ions, small molecules, proteins, and cells. Their performance can be improved through integration with other organic or inorganic nanomaterials. To further enhance their biological properties, various chemically modified nucleic acid analogues can be generated by modifying their phosphodiester backbone, sugar moiety, nucleobase, or combined sites. Alternatively, using nucleic acids as building blocks for self-assembly of highly ordered nanostructures would enhance their biological stability and cellular uptake efficiency. In this review, we will focus on the development and biomedical applications of structural and functional natural nucleic acids, as well as the chemically modified nucleic acid analogues over the past ten years. The recent progress in the development of functional nanomaterials based on self-assembled DNA-based platforms for gene regulation, biosensing, drug delivery, and therapy will also be presented. We will then summarize with a discussion on the advanced development of nucleic acid research, highlight some of the challenges faced and propose suggestions for further improvement.

Nucleic-Acid-Based Targeted Degradation in Drug Discovery

“…Nucleic acids have potential utilities in a variety of biomedical applications, including gene regulation, disease therapy, and drug delivery . Recently, nucleic-acid-based drugs are emerging as a new generation of therapeutic agents.…”

“…Recently, nucleic-acid-based drugs are emerging as a new generation of therapeutic agents. Clinically available nucleic acid drugs or candidate drugs in clinical trials mainly include antisense oligonucleotide (ASO), siRNA, aptamer, and plasmid nucleic acid drugs. , Nucleic acid drugs have the advantages of low toxicity, high specificity, and high efficiency, demonstrating their great potential in the biomedicine field.…”

Cellular uptake, tissue penetration, biodistribution, and biosafety of threose nucleic acids: Assessing in vitro and in vivo delivery

“…To improve the nuclease resistance, duplex-forming ability, and pharmacokinetic properties, scientists also put great effort into the chemical modification of the phosphodiester backbone, sugar moiety, or nucleobases of natural nucleic acids [ 12 , 13 ]. So far, a number of modified ASO analogues such as phosphorothioate oligonucleotides, peptide nucleic acids (PNAs), locked nucleic acids (LNAs), phosphorodiamidate morpholino oligomers, etc.…”

Functional Xeno Nucleic Acids for Biomedical Application

“…Chemical modification is a vital method to develop useful nucleic acid with additional properties [12][13][14] . So far, it has been used to synthesize and investigate nucleic acid analogues with modifications at nucleotide backbone, bases and sugar [15] .…”

“…XNAs refer to a class of nucleic acid analogues with sugar moiety modification(Fig. 1) [15] , which significantly enlarged the functions of nucleic acids in biotechnology and nanomedicine fields by altering the inherent properties of natural DNA/RNA [18] . For example, a kind of RNA that adds a methyl group in the 2′-hydroxy of native ribosel is named 2′-Omethyl(2′-OMe) RNA.…”