Affiliation:
1. Department of Chemistry and State Key Laboratory of Marine Pollution City University of Hong Kong Hong Kong SAR 999077 China
2. Department of Biomedical Sciences College of Veterinary Medicine and Life Sciences City University of Hong Kong Hong Kong SAR 999077 China
3. Shenzhen Research Institute of City University of Hong Kong Shenzhen 518057 China
Abstract
AbstractRNA G‐quadruplexes (D‐rG4s) are prevalent in the transcriptome and play crucial regulatory roles in various biological processes. Recently, L‐RNA aptamers have been reported to recognize functional rG4s with a strong binding affinity and specificity. However, owing to the poor cell penetration capacity of L‐RNA aptamers, their biological applications are currently limited. Herein, we rationally design an L‐RNA aptamer‐peptide conjugate, Tamra_Ahx_R8_L‐Apt.4‐1c, which can efficiently translocate into the cytosol and target the rG4 of interest. Notably, we demonstrate diverse regulatory roles of Tamra_Ahx_R8_L‐Apt.4‐1c on rG4 motif present in different regions of mRNAs and further expand the application in different cell lines. Our novel and biocompatible conjugate enhances the cellular uptake of the L‐RNA aptamer, and our robust strategy enables non‐canonical RNA structures to be targeted by L‐RNA aptamers for gene control in cells.