2025/10/23 by Jean‐Paul Desaulniers, Jean-Paul Desaulniers, Matthew L. Hammill +10 · 2 citations
Biochemistry, Genetics and Molecular Biology · #Advanced biosensing and bioanalysis techniques #Argonaute #Gene #Gene expression #Gene silencing #Nuclease #Nucleic acid #RNA #RNA Interference and Gene Delivery #RNA and protein synthesis mechanisms #RNA interference #Small interfering RNA
paper · doi:10.1021/acs.jmedchem.5c01648
published in Journal of Medicinal Chemistry 68(21), 22650-22664 (American Chemical Society)
openalex created_date 2025/10/23 · openalex publication_date 2025/10/23 · openalex updated_date 2026/08/01
Short activating RNAs (saRNAs) are short duplex RNAs that activate genes in the nucleus of the cell. This induces gene activation, or RNA activation (RNAa), which upregulates gene expression. This activation is in direct contrast to short interfering RNAs (siRNAs), which downregulate gene expression through the activation of Argonaute 2 within the RNA-induced silencing complex (RISC). siRNA chemical modifications such as 2'-O-Me, 2'-F, locked nucleic acids (LNA), unlocked nucleic acids (UNA), and backbone modifications such as phosphorothioate (PS) have been well documented and studied. In this study, a library of chemically modified saRNAs was synthesized and evaluated for their ability to activate gene expression. We have identified that a thermally destabilizing abasic carbon-based linker within the central region of the sense strand, in conjunction with an affinity-enhancing nucleoside, LNA, on the antisense strand, offers optimal duplex melting temperature, nuclease stability, and enhanced gene activation.