Synthesis and application of stimulus-triggered cyclic caged oligonucleotides for gene expression regulation

Cyclically caged oligonucleotides are a distinct category of altered biomacromolecules. They are created by incorporating caged motifs into oligonucleotides and subsequently undergoing cyclization through chemical or enzymatic means. The cyclic structure of these oligonucleotides significantly affects their characteristics and functionality, resulting in enhanced ribonuclease stability and loss of the ability to form complementary base pairs. However, when a specific stimulus is introduced, the ring structure can be deactivated, thereby restoring the oligonucleotide's function. This enables precise regulation of gene expression in both space and time by triggering a designated stimulus. In recent years, various cyclization strategies have been employed to modify antisense oligodeoxynucleotides, siRNAs, and gRNAs. This review will delve into the main synthesis methods used to generate cyclically caged oligonucleotides in the past decade. Moreover, we will explore the applications of these oligonucleotides in gene expression regulation, encompassing gene silencing and gene editing. This offers a valuable tool for comprehending the role of genes in the processes of biological growth and development.