Rational Design of L-RNA Aptamer-Peptide Conjugate for Efficient Cell Uptake and G-quadruplex-Mediated Gene Control.

Autor: Zhang K; Department of Chemistry and State Key Laboratory of Marine Pollution, City University of Hong Kong, Hong Kong SAR, 999077, China., Nie Q; Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong SAR, 999077, China., Chi-Kong Lau T; Shenzhen Research Institute of, City University of Hong Kong, Shenzhen, 518057, China.; Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong SAR, 999077, China., Kit Kwok C; Department of Chemistry and State Key Laboratory of Marine Pollution, City University of Hong Kong, Hong Kong SAR, 999077, China.; Shenzhen Research Institute of, City University of Hong Kong, Shenzhen, 518057, China.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Feb 26; Vol. 63 (9), pp. e202310798. Date of Electronic Publication: 2024 Jan 22.
DOI: 10.1002/anie.202310798
Abstrakt: RNA 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.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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