Chemical modification of PS-ASO therapeutics reduces cellular ... - Nature
Apr 29, 2019 · Here, we report that toxic gapmer PS-ASOs containing modifications such as constrained ethyl (cEt), locked nucleic acid (LNA) and 2′- O -methoxyethyl (2′-MOE) bind many …
Structure and Nuclease Resistance of 2′,4′-Constrained 2′-O ...
Combining the structural elements of the second generation 2′- O -methoxyethyl (MOE) and locked nucleic acid (LNA) antisense oligonucleotide (AON) modifications yielded the highly …
Synthesis and Biophysical Evaluation of 2′,4′-Constrained 2′
Feb 8, 2010 · We have recently shown that combining the structural elements of 2′O-methoxyethyl (MOE) and locked nucleic acid (LNA) nucleosides yielded a series of nucleoside modifications …
Ionis的第2.5代反义寡核苷酸药物 - TiPLab
在之前讲Inotersen的文章中，我们提到Ionis的第二代MOE gapmer反义寡核苷酸 (ASO)药物，其中MOE和gapmer修饰分别是为了提高寡核苷酸药物的药代动力学和效能。 cEt ( (S)-constrained …
Beyond ribose and phosphate: Selected nucleic acid modifications …
The higher stabilization of RNA can be attributed to the preorganization of LNA nucleosides towards formation of A-form duplexes , whereas in DNA duplexes LNA residues steer the …
Drug Discovery Perspectives of Antisense Oligonucleotides
PS linkages stabilize ASOs against nuclease activity, increasing their plasma half-life to up to 1 h. Chemical modification of the 2′ position with MOE, cEt, or LNA eliminates exonuclease …
Antisense oligonucleotides | Neurology Genetics
Apr 1, 2019 · cET = contrained ethyl; MOE = 2′ O -methoxyethyl; LNA = locked nucleic acid. Please see the text for descriptions of the structures. Modifications to the oligonucleotide …
A Sensitive In Vitro Approach to Assess the Hybridization …
Mar 2, 2018 · Some 2′-sugar modifications, including locked nucleic acid (LNA) and constrained ethyl (cEt) substitutions, significantly increase the binding affinity of RNase H1-activating …
Nucleic acid binding proteins affect the subcellular distribution of ...
Oct 10, 2017 · Each MOE or OMe modification increases the melting temperature of an ASO–RNA duplex by 0.5–1°C, whereas F and 2′4’-bridged nucleic acids such as LNA and cEt …
Design, synthesis and evaluation of constrained methoxyethyl ... - PubMed
Biophysical evaluation revealed that the cMOE and cEt modifications hybridize complementary nucleic acids with the same affinity as LNA while greatly increasing nuclease stability.