Multivalent Lactobionic Acid and N-Acetylgalactosamine-Conjugated Peptide Nucleic Acids for Efficient In Vivo Targeting of Hepatocytes.

ABSTRACT: Peptide nucleic acids (PNAs) are used/applied in various studies to target genomic DNA and RNA to modulate gene expression. Non-specific targeting and rapid elimination always remain a challenge for PNA-based applications. Here, the synthesis, characterization, in vitro and in vivo study of di lactobionic acid (diLBA) and tris N-acetyl galactosamine (tGalNAc) conjugated PNAs for liver-targeted delivery are reported. For proof of concept, diLBA, and tGalNAc conjugated PNAs (anti-miR-122 PNAs) were synthesized to target microRNA-122 (miR-122) which is over-expressed in the hepatic tissue. Different lengths of anti-miR-122 PNAs conjugated with diLBA and tGalNAc are tested. Cell culture and in vivo analyses to determine biodistribution, efficacy, and toxicity profile are performed. This work i

SUBMITTER: Kumar V 

PROVIDER: S-EPMC10175146 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature