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- W4315874308 abstract "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 indicates that diLBA conjugates show significant retention in hepatocytes in addition to tGalNAc conjugates after in vivo delivery. Full‐length PNA conjugates show significant downregulation of miR‐122 levels and subsequent de‐repression of its downstream targets with no evidence of toxicity. The results provide a robust framework for ligand‐conjugated delivery systems for PNAs that can be explored for broader biomedical applications." @default.
- W4315874308 created "2023-01-13" @default.
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- W4315874308 date "2023-01-20" @default.
- W4315874308 modified "2023-10-01" @default.
- W4315874308 title "Multivalent Lactobionic Acid and N‐Acetylgalactosamine‐Conjugated Peptide Nucleic Acids for Efficient In Vivo Targeting of Hepatocytes" @default.
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- W4315874308 doi "https://doi.org/10.1002/adhm.202202859" @default.
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- W4315874308 hasPublicationYear "2023" @default.
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