PMID- 20567772
OWN - NLM
STAT- MEDLINE
DCOM- 20100914
LR  - 20110516
IS  - 1742-2051 (Electronic)
IS  - 1742-2051 (Linking)
VI  - 6
IP  - 5
DP  - 2010 May
TI  - Utilization of unlocked nucleic acid (UNA) to enhance siRNA performance in vitro 
      and in vivo.
PG  - 862-70
LID - 10.1039/b918869j [doi]
AB  - Small interfering RNAs (siRNAs) are now established as a favourite tool to reduce 
      gene expression by RNA interference (RNAi) in mammalian cell culture. However, 
      limitations in potency, duration, delivery and specificity of the gene knockdown 
      (KD) are still major obstacles that need further addressing. Recent studies have 
      successfully improved siRNA performance by the introduction of several types of 
      chemical modifications. Here we explore the effect of incorporating unlocked 
      nucleic acid (UNA) into siRNA designs. The acyclic UNA monomers lack the 
      C2'-C3'-bond of the RNA ribose ring and additively decrease nucleic acid duplex 
      thermostability. We show that UNA-modifications of siRNAs are compatible with 
      efficient RNAi and can improve siRNA performance both in vitro and in vivo. In 
      particular, we find that the destabilizing properties of UNA are well suited to 
      enhance the potency of siRNAs which are heavily modified by other chemical 
      modifications such as locked nucleic acid (LNA), C4'hydroxymethyl-DNA (HM), 
      2'-O-methyl-RNA (OMe), DNA and 2'-Flouro-DNA (F). Interestingly, we find that 
      naked, but UNA-modified siRNAs have dramatically increased biostability in mice 
      and can induce potent KD in a xenograft model of human pancreas cancer. Hereby 
      UNA constitutes an important type of chemical modification for future siRNA 
      designs.
FAU - Laursen, Maria B
AU  - Laursen MB
AD  - Department of Molecular Biology, Aarhus University, DK-8000 Aarhus, Denmark.
FAU - Pakula, Malgorzata M
AU  - Pakula MM
FAU - Gao, Shan
AU  - Gao S
FAU - Fluiter, Kees
AU  - Fluiter K
FAU - Mook, Olaf R
AU  - Mook OR
FAU - Baas, Frank
AU  - Baas F
FAU - Langklaer, Niels
AU  - Langklaer N
FAU - Wengel, Suzy L
AU  - Wengel SL
FAU - Wengel, Jesper
AU  - Wengel J
FAU - Kjems, Jorgen
AU  - Kjems J
FAU - Bramsen, Jesper B
AU  - Bramsen JB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100209
PL  - England
TA  - Mol Biosyst
JT  - Molecular bioSystems
JID - 101251620
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Humans
MH  - Liver Neoplasms/therapy
MH  - Mice
MH  - Molecular Structure
MH  - RNA Interference
MH  - RNA Stability/genetics
MH  - RNA, Small Interfering/*chemistry/*genetics
MH  - Xenograft Model Antitumor Assays
EDAT- 2010/06/23 06:00
MHDA- 2010/09/15 06:00
CRDT- 2010/06/23 06:00
PHST- 2010/06/23 06:00 [entrez]
PHST- 2010/06/23 06:00 [pubmed]
PHST- 2010/09/15 06:00 [medline]
AID - 10.1039/b918869j [doi]
PST - ppublish
SO  - Mol Biosyst. 2010 May;6(5):862-70. doi: 10.1039/b918869j. Epub 2010 Feb 9.