title: Systematic chemical modifications of single stranded siRNAs significantly improved CTNNB1 mRNA silencing.
abstract: Single-stranded silencing RNAs (ss siRNA), while not as potent as duplex RNAs, have the potential to become a novel platform technology in RNA interference based gene silencing by virtue of their simplicity and plausibly favorable characteristics in pharmacokinetics and biodistribution. Like other therapeutic pharmaceutical agents, ss siRNA can be optimized to achieve higher potency through a structure-activity based approach. Systematic chemical modification at each position of a 21-mer oligonucleotide identified 2',5'-linked 3'-deoxythymidine (3dT) at position 1 and locked nucleic acids (LNAs) at the seed region as key components to afford significant enhancement in knockdown activity both in vitro and in vivo. Further optimization by additional chemical modifications should enable ss siRNA as an alternative gene silencing modality.
authors: Discovery Chemistry, Merck Research Laboratories, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, United States. Electronic address: wonsuk.chang@merck.com.
authors: Wonsuk
authors: W
authors: Chang
authors: RNA Biology, Merck Research Laboratories, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, United States.
authors: Yi
authors: Y
authors: Pei
authors: Discovery Chemistry, Merck Research Laboratories, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, United States.
authors: Erin N
authors: EN
authors: Guidry
authors: Process Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, United States.
authors: Daniel
authors: D
authors: Zewge
authors: Process Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, United States.
authors: Craig A
authors: CA
authors: Parish
authors: Structural Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, United States.
authors: Edward C
authors: EC
authors: Sherer
authors: RNA Biology, Merck Research Laboratories, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, United States.
authors: Jillian
authors: J
authors: DiMuzio
authors: RNA Biology, Merck Research Laboratories, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, United States.
authors: Hangchun
authors: H
authors: Zhang
authors: RNA Biology, Merck Research Laboratories, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, United States.
authors: Victoria J
authors: VJ
authors: South
authors: RNA Biology, Merck Research Laboratories, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, United States.
authors: Walter R
authors: WR
authors: Strapps
authors: RNA Biology, Merck Research Laboratories, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, United States.
authors: Laura
authors: L
authors: Sepp-Lorenzino
authors: Discovery Chemistry, Merck Research Laboratories, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, United States.
authors: Steven L
authors: SL
authors: Colletti
authors: Process Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, United States.
authors: Matthew G
authors: MG
authors: Stanton
mesh_terms: D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics*
chemical_list: C495270:CTNNB1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051176:beta Catenin
keywords: Chemical modification; Oligonucleotide; RNA interference; Single stranded siRNA