Novel diamine-scaffold based N-acetylgalactosamine (GalNAc)-siRNA conjugate: synthesis and in vivo activities.
RSC Adv
; 14(25): 17461-17466, 2024 May 28.
Article
em En
| MEDLINE
| ID: mdl-38818366
ABSTRACT
GalNAc-conjugated siRNA has shown remarkable potential in liver-targeted delivery in recent years. In general, tetrahydroxymethylmethane or other branching clusters constitute the basis of GalNAc's structure, which yields trivalent or tetravalent ligands. A novel diamine-scaffold GalNAc conjugate was synthesized and evaluated for its efficiency in siRNA administration. It exhibits comparable siRNA delivery effectiveness to a GalNAc NAG37 phase II clinical drug candidate targeting ANGPTL3. In addition, it exhibits more powerful silencing activity when connected to the 3'-end of the sense strand with an additional PS-linkage instead of a PO linkage between the ligand and the oligomer compared to a GalNAc L96 standard targeting TTR. Taken together, the incorporation of a diamine-scaffold into the GalNAc conjugate structure has potential in the field of gene therapy.
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01-internacional
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MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article