Chemistry of locked nucleic acids (LNA): Design, synthesis, and bio-physical properties

Wengel, Jesper; Petersen, Michael; Frieden, Miriam; Koch, Troels

doi:10.1007/bf02484561

Cited by 26 publications

(39 citation statements)

References 53 publications

(60 reference statements)

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“…When oligomers containing it are compared with other oligonucleotides, they have better thermal stability, higher molecular hybridization capability, and stronger resistance to nuclease degradation (Wengel et al, 2003;Inohara et al, 2004;Elmén et al, 2005;Castoldi et al, 2006;Rapozzi et al, 2006;Swayze et al, 2007). Therefore, it has broad application prospects.…”

Section: Introductionmentioning

confidence: 99%

Antiviral effect of hepatitis B virus S/C gene loci antisense locked nucleic acid on transgenic mice in vivo

Yb¹,

Hj²,

Yh³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. We investigated the effects of hepatitis B virus (HBV) S/C double gene loci antisense locked nucleic acid on replication and expression of HBV in hepatitis transgenic mice. HBV mice (N = 30) were randomly divided into five groups of six mice: 5% glucose solution control, empty liposome control, single-target S, single-target C, and dual-target SC groups. An antisense locked nucleic acid fragment was injected into the mice. Serum HBsAg, serum HBV DNA, HBV C-mRNA expression in liver tissue, HbsAg and HbcAg expression in hepatocytes, serum albumin, alanine transaminase (ALT), urea nitrogen, and creatinine were detected. Liver and kidney sections were examined for the effects of antisense locked nucleic acid. The expression of HBsAg was markedly inhibited; the inhibition rates of the S, C, and SC target groups were 36.63, 31.50, and 54.87%, respectively; the replication of HBV DNA was also inhibited: 23.97, 21.13, and 35.83%, respectively. After injection at 1, 3, and 5 days, the corresponding rates for HBsAg inhibition were 14.40, 25.61, and 31.33%, and for HBV DNA inhibition they were 11.04, 19.24, and 24.13%. Compared with the control group, the differences in serum albumin, ALT, urea nitrogen, 10087-10095 (2015) and creatinine in each group were not statistically significant, and the number of HbsAg-and HBcAg-positive cells in the mouse liver was significantly reduced. The liver and kidney tissues were normal. The gene therapy had significant inhibitory effects on the replication and expression of HBV in transgenic mice, and double-gene targeting was better than single-gene targeting.

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Section: Introductionmentioning

confidence: 99%

Antiviral effect of hepatitis B virus S/C gene loci antisense locked nucleic acid on transgenic mice in vivo

Yb¹,

Hj²,

Yh³

et al. 2015

Genet. Mol. Res.

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“…When use of a much shorter probe is desired because the RNA in question is very short (e.g., microRNA, 22nt) or differs from related RNAs only in a short region (as in closely related genes or alternatively spliced RNA variants), the probe must be specifically engineered for stability and detection. Locked Nucleic Acids (LNAs) are an RNA nucleotide analogue that exhibits superior specificity, hybridization kinetics, and biostability [1–6]. LNAs contain a methylene bridge between the 2′O and the 4′C on the ribose ring that ‘locks’ the ring into a high binding-affinity, RNA-mimicking conformation.…”

Section: Introductionmentioning

confidence: 99%

LNA-Based In Situ Hybridization Detection of mRNAs in Embryos

Darnell

Antin

2014

Methods in Molecular Biology

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Summary In situ hybridization (ISH) in embryos allows the visualization of specific RNAs as a readout of gene expression during normal development or after experimental manipulations. ISH using short DNA probes containing Locked Nucleic Acid nucleotides (LNAs) holds the additional advantage of allowing the detection of specific RNA splice variants, or of closely related family members that differ in only short regions, creating new diagnostic and detection opportunities. Here we describe methods for using short (14–24 nt) DNA probes containing LNA nucleotides to detect moderately to highly expressed RNAs in whole chick embryos during the first five days of embryonic development. The protocol is easily adaptable for use with embryos of other vertebrate species.

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“…Locked nucleic acids (LNAs) are modified nucleotides that contain a methylene bridge between the 29O and the 49C on the ribose ring that ''locks'' the structure into a high binding-affinity, RNA-mimicking conformation (Koshkin et al 1998;Wengel et al 2003). DNA oligonucleotide probes containing LNAs at every third position (LNA probes) show dramatically enhanced hybridization specificity and duplex stability (Mctigue et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Whole mount in situ hybridization detection of mRNAs using short LNA containing DNA oligonucleotide probes

Darnell¹,

Stanislaw²,

Kaur³

et al. 2010

RNA

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In situ hybridization is widely used to visualize transcribed sequences in embryos, tissues, and cells. For whole mount detection of mRNAs in embryos, hybridization with an antisense RNA probe is followed by visual or fluorescence detection of target mRNAs. A limitation of this approach is that a cDNA template of the target RNA must be obtained in order to generate the antisense RNA probe. Here we investigate the use of short (12-24 nucleotides) locked nucleic acid (LNA) containing DNA probes for whole mount in situ hybridization detection of mRNAs. Following extensive protocol optimization, we show that LNA probes can be used to localize several mRNAs of varying abundances in chicken embryos. LNA probes also detected alternatively spliced exons that are processed in a tissue specific manner. The use of LNA probes for whole mount in situ detection of mRNAs will enable in silico design and chemical synthesis and will expand the general use of in situ hybridization for studies of transcriptional regulation and alternative splicing.

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Chemistry of locked nucleic acids (LNA): Design, synthesis, and bio-physical properties

Cited by 26 publications

References 53 publications

Antiviral effect of hepatitis B virus S/C gene loci antisense locked nucleic acid on transgenic mice in vivo

Antiviral effect of hepatitis B virus S/C gene loci antisense locked nucleic acid on transgenic mice in vivo

LNA-Based In Situ Hybridization Detection of mRNAs in Embryos

Whole mount in situ hybridization detection of mRNAs using short LNA containing DNA oligonucleotide probes

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