Enhancing RNA inhibitory activity using clamp-G-modified nucleobases.

ABSTRACT: We explore the potential of clamp-G nucleobase-modified peptide nucleic acids (cGPNAs) as microRNA and messenger RNA inhibitors. For proof of concept, we target miR-155, which is upregulated in diffuse large B cell lymphoma. cGPNA shows significant downregulation of miR-155 and the upregulation of its downstream targets in multiple lymphoma cell lines. Also, cGPNA treatment in vivo reduced tumor growth and improved survival in the U2932 cell-derived xenograft mouse model. To assess the broad application of cGPNA as an antisense modality, we also target transthyretin (TTR) mRNA. We establish a dose-dependent effect of antisense cGPNA on TTR mRNA levels. For in vivo studies, we conjugated cGPNA-based TTR antisense with lactobionic acid-based targeting ligand for <

SUBMITTER: Pradeep SP 

PROVIDER: S-EPMC11484553 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature