ライフサイエンスコーパス: gapmer

1 '-O-methoxyethyl (2'-O-ME) phosphorothioate 'gapmer'.

2 hepatoxicity observed with some LNA-modified gapmers.

3 Antisense oligonucleotide Fli-1 Gapmer administered via intrahippocampal injection decel

4 silencing via the antisense oligonucleotide GapmeR ameliorated anxiety-like behavior and cognitive i

5 acy, BalbC mice were treated with 2'-O-DMAOE gapmers and a dose-dependent reduction in the targeted C

6 leotide consisting of a phosphorothioate DNA-gapmer antisense oligonucleotide (ASO) strand and its co

7 d this theory by central administration of a gapmer antisense oligonucleotide (ASO) targeting Scn2a m

8 ith intrathecally administered elsunersen, a gapmer antisense oligonucleotide targeting SCN2A, in a f

9 ), enhances the potency of second-generation gapmer antisense oligonucleotides (ASOs) 6-10-fold in mo

10 stability and protein binding properties of gapmer antisense oligonucleotides (ASOs) and is one of v

11 show that gene targeting 2'-O-methyl (2'OMe) gapmer antisense oligonucleotides (ASOs) can have opposi

12 We recently showed that 2'-O-methyl (2'OMe) gapmer antisense oligonucleotides (ASOs) exhibited seque

13 orothioate (PS)-modified tricycloDNA (tcDNA) gapmer antisense oligonucleotides (ASOs) in T(m), cell c

14 e a series of phosphorothioate (PS)-modified gapmer antisense oligonucleotides (ASOs) with control of

15 OE second generation ASOs, we have evaluated gapmer antisense oligonucleotides containing BNAs having

16 In contrast, similarly targeted MOE-gapmer antisense oligonucleotides that degrade RNA but d

17 ownregulation was achieved in vivo through a gapmer approach.

18 We show that all PS linkages in a gapmer ASO can be replaced with MsPA without compromisin

19 A human SCN2A gapmer ASO could likewise impact the lives of patients w

20 2.) In an animal experiment, a 16-mer F-CeNA gapmer ASO showed similar RNA affinity but significantly

21 al Drug Administration (FDA) approval of the GapmeR ASO targeting SOD1, tofersen.

22 This non-gapmer ASO-induced mRNA reduction was observed for diffe

23 in PC4, in complex with a full PS 2'-OMe DNA gapmer ASO.

24 ver compared with the parent single-stranded gapmer ASO.

25 de gap region of toxic phosphorothioate (PS) gapmer ASOs can enhance therapeutic index and safety.

26 creening of fully phosphorothioated (PS)-LNA gapmer ASOs designed against the BACH1 transcript.

27 mproving the cellular uptake and activity of gapmer ASOs in sortilin expressing cells (sixfold) and i

28 region can enhance the potency and safety of gapmer ASOs modified with high-affinity constrained Ethy

29 strate that intratracheally administered LNA gapmer ASOs robustly induce gene silencing in lung fibro

30 However, many phosphorothioate (PS)-modified gapmer ASOs show transient motor phenotypes when injecte

31 We designed and chemically optimized gapmer ASOs targeting specific sequences at the start of

32 Surprisingly, TLR8 potentiation by the gapmer ASOs was blunted by locked nucleic acid (LNA) and

33 S-cEt (S-2'-O-Et-2',4'-bridged nucleic acid) gapmer ASOs, approximately 60-fold enhancement in potenc

34 Gapmer ASOs, targeting the S331F variant in either 2'-O-

35 Reducing the PS content of gapmer ASOs, which contain a stretch of PS-DNA, improves

36 r eliminated toxicity of several hepatotoxic gapmer ASOs.

37 rmacological and toxicological properties of gapmer ASOs.

38 BMECs) were cultured and treated with Malat1 GapmeR before 16 h oxygen and glucose depravation (OGD).

39 We have shown that the ASO gapmers can interact with the Ago-2 PAZ domain and can l

40 n of DICER or AGO2 using either siRNA or MOE-gapmer chemistries resulted in the induction of DUX4 exp

41 We designed chimeric ASOs, termed gapmers, containing modified nucleic acid residues to in

42 avage patterns (both human and E. coli) in a gapmer context.

43 HNA and 2'-O-ME gapmers displayed similar potency, but a pure HNA antise

44 A DNA/locked nucleotide acid gapmer duplex with an alpha-tocopherol-conjugated comple

45 While gapmers efficiently knock down as well as terminate tran

46 ncing of MALAT1 by small interfering RNAs or GapmeRs induced a promigratory response and increased ba

47 ing of MANTIS with small interfering RNAs or GapmeRs inhibited angiogenic sprouting and alignment of

48 RRA levels using a locked nucleic acid (LNA) GapmeR led to large nuclear VR aggregates.

49 Thus, HNA gapmers may provide a valuable additional tool for antis

50 Fli-1 Gapmer-mediated inhibition of Fli-1 protected against Ab

51 Finally, gapmer-mediated knockdown of HSATII transcripts depleted

52 GapmeR-mediated knockdown of nuclear MYRACL disrupted OL

53 otential of HERNA1 inhibition was studied in gapmer-mediated loss-of-function studies in vitro using

54 GapmeR-mediated silencing of Meg3 in CFs resulted in the

55 ite-specific antisense oligonucleotides (LNA-GapmeRs) not only markedly decreased proliferation and m

56 red the antisense effects of a chimeric HNA 'gapmer' oligonucleotide comprising a phosphorothioate ce

57 'Gapmer' oligonucleotides have one or two 2'-O-modified r

58 (MsPA) linkages in the DNA gap and flanks of gapmer PS ASOs and characterized the effect of these lin

59 Here, we report that toxic gapmer PS-ASOs containing modifications such as constrai

60 Pharmacological inhibition of MALAT1 by GapmeRs reduced blood flow recovery and capillary densit

61 Treatment with anti-MDR1 HNA gapmer resulted in increased cellular accumulation of th

62 The gapmers selectively knockdown expanded CUG transcripts a

63 Silencing of Malat1 by Malat1 GapmeR significantly increased OGD-induced cell death an

64 se model, we showed that our designed 2'-MOE gapmers significantly reduced DUX4 transcript levels in

65 tive cytoplasmic mechanism through which ASO gapmers silence their targets when transfected or delive

66 that Pol II termination is not observed with gapmers targeting the 3' terminal portions of the transc

67 oses, we validated the use of an anti-uPARAP gapmer to induce a labyrinthine vasculature and attenuat

68 inhibited with antisense locked nucleic acid-GapmeRs to examine its function.

69 nistration of FII antisense oligonucleotide "gapmer" to Berkeley SCD mice to selectively reduce circu

70 D using antisense 2'-O-methoxyethyl (2'-MOE) gapmers, to knock down DUX4 mRNA expression.

71 -methyluracil nucleoside (S)-cEt-BNA, a key "gapmer" unit in a number of biologically relevant antise

72 The anti-MDR1 HNA gapmer was substantially more potent than a phosphorothi

73 Furthermore, combination of gapmers with morpholino ASOs that help release binding o

74 The phosphorothioate oligonucleotide 'gapmers', with 2'-O-DMAOE- modified nucleoside residues