ライフサイエンスコーパス: ASO

1 ASO binding also induces the formation of a dimer of dim

2 ASO length and chemical modification influenced the effi

3 ASO therapeutics are chemically modified and include pho

4 ASO treatment led to decreased Abeta pathology and impro

5 ASO treatment results in long-term improvement in CFTR a

6 ASO treatment was tested in a conditional mouse model wi

7 ASO was administered by intracerebroventricular injectio

8 ASOs also induced exon skipping in cell lines derived fr

9 ASOs are small synthetic single-stranded chains of nucle

10 ASOs are typically 15-25 nt long and considered to be hi

11 ASOs can reduce the levels of mutant proteins by breakin

12 oved potency of DMPK, Cav3, CD36 and Malat-1 ASOs (3- to 7-fold) in mouse muscle.

13 cleavage of hepatic VEGF using either MMP-9 ASO or intraportal MMP inhibitor in 5-week and 10-week H

14 Activity of fatty acid ASO conjugates correlated with the affinity to albumin a

15 difficult to reduce with RNase H1 activating ASOs and some ASOs display a shorter duration of activit

16 ioavailability of intrathecally administered ASOs.FUNDINGSMA Foundation, SMART, NIH (R01-NS096770, R0

17 e or whether modulation of autophagy affects ASO activity and localization.

18 illustrated by recent findings that altering ASO chemical modifications dramatically improves therape

19 JCI, Klein et al. showed that conjugating an ASO with an arginine-rich cell-penetrating peptide, Pip6

20 We test an ASO targeting the CFTR c.3718-2477C>T mutation and show

21 Our results demonstrate that an ASO pharmacotherapeutic administered to a developing org

22 This is the first time that an ASO targeting a non-CUG sequence within the DMPK 3'UTR h

23 In addition, we used an ASO targeting murine HK2 (mHK2-ASO1) to validate the saf

24 Apoc3 ASO treatment abolished the increased hepatic Apoc3 expr

25 Treatment of mice with an ATXN2 ASO also modified innate immunity, the complement system

26 o different antisense oligonucleotide-based (ASO-based) therapies are currently in clinical use to tr

27 n human and rodent neurons, CGG RAN-blocking ASOs suppressed repeat toxicity and prolonged survival.

28 tion of these proteins to LEs is mediated by ASO-protein interactions.

29 n skipping of mdx-type exon 23 is induced by ASOs.

30 We found that certain ASOs targeting the coding region of some mRNAs that init

31 a potent and selective therapeutic KRAS cEt-ASO currently under clinical development for the treatme

32 e used this to investigate mechanisms of cEt-ASO trafficking across a panel of cancer cells.

33 These next-generation cEt-ASOs can enter cells without transfection reagents.

34 s novel insights into the trafficking of cEt-ASOs and mechanisms that may determine their cellular fa

35 intracellular uptake and trafficking of cEt-ASOs leading to successful target knockdown are highly c

36 and determined the influence of ASO charge, ASO length, peptide charge, linker chemistry and ligand

37 e significantly reduced with mixed-chemistry ASOs of the same sequence.

38 We found that cholesterol ASO conjugates showed 5-fold potency enhancement in the

39 Chronic ASO-mediated suppression of PrP beginning at any time up

40 Administration of palmitic acid-conjugated ASO (Palm-ASO) in mice results in a rapid and substantia

41 he BRET donor, to a fluorescently conjugated ASO acting as the BRET acceptor.

42 ased tissue accumulation of lipid conjugated ASO is isolated to the interstitium.

43 strate that the activity of lipid conjugated ASO was reduced in two mouse models with defects in endo

44 urated and unsaturated fatty acid conjugated ASOs with a range of hydrophobicity.

45 ontrast, palmitate and tocopherol-conjugated ASOs showed enhanced potency in the skeletal muscle of r

46 ntracerebroventricular Ncald-ASO3 or control-ASO injection were presymptomatically administered in a

47 ter ASOs, combining two ASOs, and delivering ASOs by free uptake also reduced off-target activity.

48 the muscle will be beneficial for developing ASO therapeutics targeting genes expressed in the muscle

49 nterstitium of the muscle tissues to enhance ASO functional uptake.

50 tage to identify other strategies to enhance ASO potency in muscle tissues.

51 hat can be used in the gap-region to enhance ASO safety and provide insights into understanding the b

52 amidate oligomer (PMO) dramatically enhanced ASO delivery into striated muscles of DM1 mice following

53 participates in and contributes to enhanced ASO activity.

54 s on plasma protein binding and on enhancing ASO potency in the muscle of rodents and monkeys.

55 ma proteins by lipid-conjugation facilitates ASO transport across endothelial barriers into tissue in

56 -CON) or ASO specific for prothrombin (FII) (ASO-FII) to yield mFFP or ASO-CON mFFP or ASO-FII mFFP.

57 Finally, ASOs with strategically placed mismatches can be used to

58 administration that have been described for ASO-based therapies.

59 ino acids that are specifically required for ASO binding interactions, and by substitution of abasic

60 se and broaden the therapeutic landscape for ASOs in the treatment of other diseases using a similar

61 efficient and high-throughput screenings for ASOs.

62 Furthermore, ASO rapidly trafficked to the late endosome/lysosome in

63 Furthermore, ASO-directed transcription termination is mediated by th

64 ons with proteins is needed to inform future ASO design efforts.

65 in complex with a full PS 2'-OMe DNA gapmer ASO.

66 This non-gapmer ASO-induced mRNA reduction was observed for different tr

67 nated toxicity of several hepatotoxic gapmer ASOs.

68 g the cellular uptake and activity of gapmer ASOs in sortilin expressing cells (sixfold) and in spina

69 can enhance the potency and safety of gapmer ASOs modified with high-affinity constrained Ethyl (cEt)

70 gical and toxicological properties of gapmer ASOs.

71 urprisingly, TLR8 potentiation by the gapmer ASOs was blunted by locked nucleic acid (LNA) and 2'-met

72 Even though RNase H ASOs can reduce the level of RNA associated with chromat

73 Here we show that RNase H ASOs targeted to introns or exons robustly reduce the le

74 , clustering of microglia revealed that IDOL-ASO treatment shifted the composition of the microglia p

75 Advances in ASO chemistry have led to the development of phosphoroth

76 tissue accumulation and similar increase in ASO activity.

77 utophagy-related trafficking participates in ASO uptake or whether modulation of autophagy affects AS

78 ation/fasting, and ketogenic diet, increased ASO-mediated target reduction in vitro and in vivo.

79 s like fatty acids and cholesterol increases ASO accumulation and activity in multiple tissues.

80 Palmitic acid conjugation increases ASO plasma Cmax and improved delivery of ASO to intersti

81 binatorial SMN-dependent and SMN-independent ASO-based therapy for SMA.

82 ing binding to plasma proteins can influence ASO activity and distribution to extra-hepatic tissues i

83 defined process for productive intracellular ASO drug delivery.

84 independent of the methods used to introduce ASOs into cells.

85 Antisense oligonucleotide knockdown (ASO-KD) of nicotinamide N-methyltransferase (NNMT) in hi

86 Limited ASO distribution to rostral spinal and brain regions in

87 Linking ASOs to cell-penetrating peptides, or even other moietie

88 be reversed by a single dose of PrP-lowering ASO administered after the detection of pathological cha

89 prove therapeutic outcomes, we microinjected ASO directly into the E12.5 inner ear.

90 ructure of the DNA-binding domain of a model ASO-binding protein PC4, in complex with a full PS 2'-OM

91 t also helps explain why some fully modified ASOs cause RNA target to be reduced despite being unable

92 rget events caused by the uniformly modified ASOs tested in this study were significantly reduced wit

93 However, whether or not splice-modulating ASOs also induce hybridization-dependent mis-splicing of

94 ed the in vitro effects of splice-modulating ASOs on 108 potential off-targets predicted on the basis

95 tion also improved the potency of morpholino ASO designed to correct splicing of survival motor neuro

96 generic applications in tests with multiple ASOs.

97 tified Ncald-ASO3-out of 450 developed Ncald ASOs-as the most efficient and non-toxic ASO for the CNS

98 ucleotides (ASO), we synthesized neurotensin-ASO conjugates and evaluated their cellular uptake and a

99 In Western diet (WD)-fed female mice, NNMT-ASO-KD reduced body weight, fat mass, and insulin level

100 Using NNMT-ASO-KD or NNMT knockout mice (NNMT(-/-)), we tested the

101 ealed decreased osteoclast numbers in Notch2 ASO-treated Notch2(tm1.1Ecan) mice.

102 Notch2 ASOs decreased the induction of mRNA levels of TNF super

103 lastogenesis, which was suppressed by Notch2 ASOs.

104 indicated that the administration of Notch2 ASOs ameliorates the cancellous osteopenia of Notch2(tm1

105 iorated by systemic administration of Notch2 ASOs.

106 n reporter system which allows us to observe ASO/protein interactions in real time in live cells, we

107 influence on protein binding or activity of ASO fatty acid conjugates.

108 The binding affinity of ASO fatty acid conjugates to plasma proteins improved wi

109 romising future regarding the application of ASO-based therapies for polyQ disorders in humans, offer

110 are difficult to predict, and the choice of ASO chemistry influences the extent of off-target activi

111 ses ASO plasma Cmax and improved delivery of ASO to interstitial space of mouse muscle.

112 with good productive uptake, distribution of ASO was perinuclear and in those with poor productive up

113 A single intra-otic dose of ASO corrects harmonin RNA splicing, restores harmonin pr

114 RNA associated with chromatin, the effect of ASO-directed RNA degradation on transcription has never

115 ue exposure in mice and reduces excretion of ASO in urine, histological review of skeletal and cardia

116 eting have resulted in a newer generation of ASO drugs that are more potent and better tolerated than

117 Here we examine in detail the impact of ASO backbone chemistry, 2'-modifications, and buffer env

118 e conjugates and determined the influence of ASO charge, ASO length, peptide charge, linker chemistry

119 bcellular localization of the interaction of ASO and PC4 in live cells.

120 Over the years, chemical optimization of ASO molecules has allowed significant improvement of the

121 e capability of simultaneous quantitation of ASO metabolites.

122 a proteins also facilitates the transport of ASO from the interstitium to the lymph and back into cir

123 albumin binding will facilitate traversal of ASO from the blood compartment to the interstitium of th

124 Our findings demonstrate the utility of ASO-based reading-frame correction as an approach to tre

125 h have been shown to enhance the affinity of ASOs for proteins, suggesting that localization of these

126 imitation for more widespread application of ASOs relates to relatively poor tissue penetration.

127 ectiveness as well as the biodistribution of ASOs for exon skipping therapy.

128 ve ligands that enhance targeted delivery of ASOs to tissues.

129 hese results demonstrate that the effects of ASOs on transcription must be considered for appropriate

130 characterizes the immumodulatory effects of ASOs to advance their therapeutic development.

131 hagy activation enhanced the localization of ASOs into autophagosomes without altering intracellular

132 istries as well as chemical modifications of ASOs.

133 istries as well as chemical modifications of ASOs.

134 ssible approach for enhancing the potency of ASOs with diverse nucleic acid modifications.

135 an improved alternative for quantitation of ASOs and metabolites in plasma and tissue samples, showi

136 The success of ASOs in several animal models, as well as encouraging re

137 However, systemic use of ASOs for this muscular disease remains challenging due t

138 Our findings demonstrate the utility of ASOs in correcting CFTR expression and channel activity

139 treatment with an antisense oligonucleotide (ASO) (ISIS 486178) targeted to a non-CUG sequence within

140 ted SMA patients, antisense oligonucleotide (ASO) concentration and full-length (exon 7 including) SM

141 re we describe an antisense oligonucleotide (ASO) directed against human HK2 (HK2-ASO1), which suppre

142 Antisense oligonucleotide (ASO) drugs that trigger RNase H1 cleavage of target RNAs

143 identification of antisense oligonucleotide (ASO) impurities using a Q-Exactive mass spectrometer.

144 ctional uptake of antisense oligonucleotide (ASO) in the muscle will be beneficial for developing ASO

145 splice-switching antisense oligonucleotide (ASO) into the amniotic cavity immediately surrounding th

146 SCA2 mice with an antisense oligonucleotide (ASO) lowering ATXN2 expression.

147 inistration of an antisense oligonucleotide (ASO) targeting mTORC2's defining component Rictor specif

148 y, nusinersen, an antisense oligonucleotide (ASO) that corrects SMN2 splicing and thereby increases f

149 treated using an antisense oligonucleotide (ASO) that induces exon skipping to restore the open read

150 .5668 G > T using antisense oligonucleotide (ASO) therapy leads to restoration of CEP290 protein expr

151 y, we utilized an antisense oligonucleotide (ASO) to reduce IDOL expression therapeutically in the br

152 Conjugation of antisense oligonucleotide (ASO) with a variety of distinct lipophilic moieties like

153 ranscript with an antisense oligonucleotide (ASO) would delay seizure onset and prolong survival in a

154 splice-switching antisense oligonucleotide (ASO), was the first approved drug to treat SMA.

155 ently showed that antisense oligonucleotide (ASO)-mediated PrP suppression extends survival and delay

156 ehicle or control antisense oligonucleotide (ASO-CON) or ASO specific for prothrombin (FII) (ASO-FII)

157 ration of Notch2 antisense oligonucleotides (ASO) down-regulates Notch2 and the Notch target genes He

158 einase 9 (MMP-9) antisense oligonucleotides (ASO) or an MMP inhibitor were used to induce liver-selec

159 uctive uptake of antisense oligonucleotides (ASO), we synthesized neurotensin-ASO conjugates and eval

160 Antisense oligonucleotides (ASOs) are chemically synthesized nucleic acid analogs de

161 l (2'OMe) gapmer antisense oligonucleotides (ASOs) can have opposing activities on Toll-Like Receptor

162 demonstrate that antisense oligonucleotides (ASOs) can reduce mRNA levels by acting through the no-go

163 e performance of antisense oligonucleotides (ASOs) has been a subject of debate for over two decades.

164 Antisense oligonucleotides (ASOs) have been under intense investigation over recent

165 Splice-switching antisense oligonucleotides (ASOs) have emerged as an effective therapeutic strategy

166 Antisense oligonucleotides (ASOs) interact with target RNAs via hybridization to mod

167 ailable for DMD, antisense oligonucleotides (ASOs) mediated exon skipping is a promising therapeutic

168 Antisense oligonucleotides (ASOs) modulate cellular target gene expression through d

169 impact of Apoc3 antisense oligonucleotides (ASOs) on lipoprotein metabolism and atherosclerosis in a

170 llular uptake of antisense oligonucleotides (ASOs) proceeds through the endocytic pathway; however, o

171 Antisense oligonucleotides (ASOs) targeting pathologic RNAs have shown promising the

172 s via the use of antisense oligonucleotides (ASOs) that harness the RNase H1 mechanism.

173 Antisense oligonucleotides (ASOs) that trigger RNase-H-mediated cleavage are commonl

174 ogies, including antisense oligonucleotides (ASOs), siRNAs, RNA-targeting clustered regularly intersp

175 ing non-cleaving antisense oligonucleotides (ASOs), we selectively blocked CGG RAN.

176 Splice-switching antisense oligonucleotides (ASOs), which bind specific RNA-target sequences and modu

177 drugs, including antisense oligonucleotides (ASOs).

178 te (PS) modified antisense oligonucleotides (ASOs).

179 ic properties of antisense oligonucleotides (ASOs).

180 ors like Tmprss6-antisense oligonucleotides [ASOs]) or increase erythropoiesis (by erythropoietin [EP

181 Through a screen of 192 2'OMe ASOs and sequence mutants, we characterized the structur

182 ng the immunosuppressive activities of 2'OMe ASOs on TLR7.

183 ence, sugar modifications, and PS content on ASO interactions with several abundant human plasma prot

184 influence of PS ASO protein interactions on ASO performance, and the structure activity relationship

185 gated the effects of autophagy modulation on ASO activity in cells and mice.

186 Both antisense only (ASO)-R-loops and sense/antisense (S/AS)-R-loops sharply

187 ntrol antisense oligonucleotide (ASO-CON) or ASO specific for prothrombin (FII) (ASO-FII) to yield mF

188 prothrombin (FII) (ASO-FII) to yield mFFP or ASO-CON mFFP or ASO-FII mFFP.

189 ) (ASO-FII) to yield mFFP or ASO-CON mFFP or ASO-FII mFFP.

190 n comparison with unconjugated PMO and other ASO strategies.

191 sed on analysis of data from two overlapping ASO sequences, we conclude that off-target effects are d

192 ration of palmitic acid-conjugated ASO (Palm-ASO) in mice results in a rapid and substantial accumula

193 potency relative to the stereorandom parent ASO or improved safety over the 2'-OMe gap-modified ster

194 the 2'-OMe gap-modified stereorandom parent ASO.

195 In particular, ASOs are frequently used to functionally interrogate lon

196 ity can modulate RNase H1 cleavage patterns, ASO sequence and design are the primary drivers which de

197 Phosphorothioate ASOs fully modified with 2'-O-methoxyethyl decreased mRN

198 s the effects of most toxic phosphorothioate ASOs (PS-ASOs).

199 n aid in the design of safer and more potent ASO drugs, as illustrated by recent findings that alteri

200 ctors mechanistically involved in productive ASO uptake, including the endosomal GTPase Rab5C.

201 Moreover, PS ASO protein interactions can affect many aspects of thei

202 d the structure activity relationships of PS ASO modification and protein interactions.

203 which PS ASOs interact, the influence of PS ASO protein interactions on ASO performance, and the str

204 ts into understanding the biochemistry of PS ASO protein interactions.

205 ummarize recent progress in understanding PS ASO protein interactions, highlighting the proteins with

206 PS ASOs were found to associate predominantly with albumin

207 nally, plasma proteins capable of binding PS ASOs in human plasma were confirmed by employing affinit

208 In contrast, PS ASOs associate predominantly with HRG in monkey plasma b

209 Modified PS ASOs display better binding affinity to the target RNAs

210 ar forces that govern the interactions of PS ASOs with cellular proteins and provide a potential mode

211 g palmitate, tocopherol or cholesterol to PS ASOs and their effects on plasma protein binding and on

212 ons, highlighting the proteins with which PS ASOs interact, the influence of PS ASO protein interacti

213 to the development of phosphorothioate (PS) ASOs with constrained-ethyl modifications (cEt).

214 etween affinity for specific proteins and PS-ASO toxicity was observed.

215 -ASO release from endosomes and decreased PS-ASO activity in human cells.

216 Reduction of M6PR levels also decreased PS-ASO activity in mouse cells and in livers of mice treate

217 achinery between LE and Golgi facilitates PS-ASO release.

218 cellular levels of GCC2 or M6PR impaired PS-ASO release from endosomes and decreased PS-ASO activity

219 proteins to nucleoli is an early event in PS-ASO toxicity, followed by nucleolar stress, p53 activati

220 cally M6PR shuttling mediated by GCC2, in PS-ASO trafficking and activity.

221 act through the same pathway to influence PS-ASO activity, with GCC2 action preceding that of M6PR.

222 To better understand the chemistry of PS-ASO interactions, we have focused on human positive cofa

223 osphorothioate antisense oligonucleotide (PS-ASO) interactions with proteins has revealed that protei

224 highly influenced by the chemistry of the PS-ASO binding environment, however little correlation betw

225 GCC2 relocated to LEs upon PS-ASO treatment, and M6PR also co-localized with PS-ASOs i

226 ivers of mice treated subcutaneously with PS-ASO, indicating a conserved mechanism.

227 ects of most toxic phosphorothioate ASOs (PS-ASOs).

228 Our data indicate that M6PR binds PS-ASOs and facilitates their vesicular escape.

229 Here, we report that toxic gapmer PS-ASOs containing modifications such as constrained ethyl

230 ew avenues for the medicinal chemistry of PS-ASOs and research on all elements of the molecular pharm

231 The activity of PS-ASOs is strongly influenced by association with both int

232 Our findings will guide the design of PS-ASOs with optimal therapeutic profiles.

233 profound influences on the interaction of PS-ASOs with specific proteins.

234 own about the chemistry of interaction of PS-ASOs with this protein.

235 lar mechanisms of action, and toxicity of PS-ASOs.

236 sphorothioate antisense oligonucleotides (PS-ASOs) are not fully understood.

237 sphorothioate antisense oligonucleotides (PS-ASOs) from late endosomes (LEs) is a rate-limiting step

238 oate-modified antisense oligonucleotides (PS-ASOs) interact with a host of plasma, cell-surface and i

239 he cells treated with toxic, but not safe PS-ASOs.

240 In addition, we have determined that PS-ASOs bind P54nrb via RRM1 and RRM2, while they bind RNas

241 s, we have determined that safe and toxic PS-ASOs associate with these proteins with kinetics and imp

242 Toxic PS-ASOs interact in a complex that includes RNase H1, P54nr

243 reatment, and M6PR also co-localized with PS-ASOs in LEs or on LE membranes.

244 n as immunotherapies, and show that rational ASO selection can be used to prevent unintended immune s

245 A single treatment with Scn8a ASO extended survival of Dravet syndrome mice from 3 wee

246 vations was further demonstrated for several ASOs versus multiple gene targets.

247 Furthermore, using shorter ASOs, combining two ASOs, and delivering ASOs by free up

248 al study, a single subcutaneous low-dose SMN-ASO and a single intracerebroventricular Ncald-ASO3 or c

249 While low-dose SMN-ASO rescues multiorgan impairment, additional NCALD redu

250 Although some ASOs induced nonsense-mediated decay, others reduced mRN

251 educe with RNase H1 activating ASOs and some ASOs display a shorter duration of activity than the pro

252 mechanism of tolerance that occurs with some ASOs.

253 methods to enhance autophagy and subsequent ASO activity using translatable approaches such as fasti

254 These results support ASO-mediated PrP lowering, and PrP-lowering therapeutics

255 cations can be effective as splice-switching ASOs in the context of SMA and potentially other disease

256 Target ASOs were extracted from biological samples by hybridiza

257 ent of neonatal mice with an exon 5-targeted ASO-induced robust exon skipping for more than a year, i

258 This indicates that exon-targeted ASOs achieve full activity after the pre-mRNA has underg

259 ASOs and, to a lesser extent, exon-targeted ASOs cause RNA polymerase II (Pol II) transcription term

260 matin to a greater extent than exon-targeted ASOs.

261 Here we show that intron-targeted ASOs and, to a lesser extent, exon-targeted ASOs cause R

262 Surprisingly, intron-targeted ASOs reduce the level of pre-mRNA associated with chroma

263 proof-of-principle data that gene-targeting ASOs can be selected to synergize with TLR8 agonists cur

264 vious findings with additional PrP-targeting ASOs, and demonstrate therapeutic benefit against four a

265 linical and clinical trials that have tested ASO therapeutics in polyQ disorders.

266 Here, we show that ASOs act upon nascent transcripts and, consequently, ind

267 Our data also shows for the first time that ASOs may be a viable option for treating cardiac patholo

268 uence, chemical nature, and structure of the ASO can have profound influences on the interaction of P

269 binds the 5'-terminal 2'-OMe PS flank of the ASO, while the other interface binds the regular PS DNA

270 f the plasma-protein binding profiles of the ASO-conjugates by size-exclusion chromatography revealed

271 nucleotides we identify the positions on the ASO that most strongly influence affinity for PC4.

272 As a result, the ASO forms a hairpin-like structure.

273 Following binding to the targeted RNA, the ASO perturbs RNA function by promoting selective degrada

274 We also show that the ASO is more effective at recovering chloride secretion i

275 Of note, we demonstrate that the ASO treatment reversed the cardiac conduction abnormalit

276 The ASOs that activated this decay pathway hybridized near t

277 se pairing between homologous regions of the ASOs bound by each dimer of PC4.

278 tified 17 mis-splicing events for one of the ASOs tested.

279 This process requires that the ASOs bind in the coding region and reduce the target mRN

280 on for developing more effective therapeutic ASOs for muscle disorders.

281 These ASO-protein interactions are highly influenced by the ch

282 activity, decreased the activities of these ASOs.

283 This ASO blockade enhanced endogenous FMRP expression in huma

284 Thus, ASO strategies for DM1 can abolish the toxic RNA gain-of

285 Targeting Tmprss6 messenger RNA by Tmprss6-ASO was proven to be effective in improving IE and splen

286 Here, we combined Tmprss6-ASO with EPO administration or removal of a single Tfr2

287 roved the anemia, the combination of Tmprss6-ASO + EPO or Tmprss6-ASO + Tfr2 single-allele deletion p

288 While administration of Tmprss6-ASO alone improved the anemia, the combination of Tmprss

289 combination of Tmprss6-ASO + EPO or Tmprss6-ASO + Tfr2 single-allele deletion produced significantly

290 ald ASOs-as the most efficient and non-toxic ASO for the CNS, by applying a stepwise screening strate

291 ically replaced anionic PS-linkages in toxic ASOs with charge-neutral alkylphosphonate linkages.

292 rthermore, using shorter ASOs, combining two ASOs, and delivering ASOs by free uptake also reduced of

293 e muscle of rodents relative to unconjugated ASOs.

294 recent years for some polyQ disorders using ASO therapeutics.

295 chanism by which mRNAs can be degraded using ASOs, adding a new antisense approach to modulation of g

296 d highest binding affinity was observed with ASO conjugates containing fatty acid chain length from 1

297 ior haemostasis versus those transfused with ASO-FII following TT, LL, or ILI.

298 Mice transfused with ASO-FII mFFP demonstrated inferior haemostasis versus th

299 days in the Scn8a-R1872W/+ mice treated with ASO.

300 Targeting the transcript 3' end with ASOs, however, allows transcript knockdown while preserv

301 The co-localization of M6PR and of GCC2 with ASOs is influenced by the PS modifications, which have b