ライフサイエンスコーパス: off-target

1 howed increased somatic hypermutation in AID off-targets.

2 n targets and clear selectivity over the two off-targets.

3 eased the activity and reduced the number of off-targets.

4 roaches in a unique way to predict potential off-targets.

5 repurposing, and the detection of potential off-targets.

6 on in irradiated tumors along with decreased off-target accumulation in visceral organs.

7 In addition, off-target actions may also contribute to its potential

8 d inhibitory synapses may have resulted from off-target actions of Cd(2+), a nonselective VACC blocke

9 rofile of other tested FAAH inhibitors, that off-target activities of BIA 10-2474 may have played a r

10 cement of serotonin efficacy, no significant off-target activities, and low binding competition with

11 he application of base editing is limited by off-target activity and reliance on intracellular DNA de

12 structural features that contribute more to off-target activity can also be very effective.

13 ge and human genomes, and explain why Cas9's off-target activity can be so high.

14 ecificity, and PAM requirements and reducing off-target activity for the development of Cas9-based th

15 gible CCR2 activity and demonstrates minimal off-target activity genome wide.

16 AID serine38 (pS38), but the role of pS38 in off-target activity has not been evaluated.

17 tivity of BLISS by assessing the genome-wide off-target activity of two CRISPR-associated RNA-guided

18 een made to further understanding of on- and off-target activity to assist the design of CRISPR-based

19 Genome-wide assessment of off-target activity using BLISS indicated that these var

20 Off-target activity was not observed.

21 In addition, through off-target activity, AID has a much broader effect on ge

22 Studies on its off-target activity, along with approaches to minimize t

23 target engagement and discern analogues with off-target activity, each compound was evaluated against

24 IV-1 gRNAs have been designed to account for off-target activity, however, they seldom account for ge

25 n terms of potency, selectivity, and reduced off-target activity.

26 the non-toxic NPs were not found to exhibit off-target activity.

27 les for designing experiments for minimizing off-target activity.

28 osine kinase inhibitor developed to minimise off-target activity.

29 ove pharmacokinetic properties and eliminate off-target activity.

30 e activity in vitro and in vivo with reduced off-target activity.

31 Although off-target AID activity also contributes to oncogenic po

32 Off-target AID association also occurs, which causes onc

33 this study was able to recognize and reduce off-target amplification in dPCR quantification, thereby

34 hanics-based approach provides more reliable off-target analyses and sgRNA design.

35 regions, thus emphasizing the importance of off-target analysis in the design of saturating-mutagene

36 analysis workflow, including normalization, off-target analysis, integration of gene expression data

37 odominant non-NAb epitopes that might induce off-target and potentially interfering responses.

38 To date, overall efficiencies, rates of off-targeting and degree of genetic mosaicism have not b

39 ese activities allow Ago2 to rapidly dismiss off-targets and dynamically search for seed-matched site

40 riment, we built a new website that predicts off-targets and helps select and clone efficient guide s

41 otospacer-adjacent motif (PAM), and possible off-targets, and scores the conservation of the deleted

42 tics, where, barring an influence from their off-target anti-inflammatory pharmacologic effects, an u

43 gen design field has been whether the latter off-target antibodies might interfere with the induction

44 e gp120 V3 region, to block the induction of off-target antibodies.

45 SEFL mutations eliminated off-target antibody-dependent monocyte phagocytosis of c

46 ations, a new web-based tool for genome-wide off-target assessment is established.

47 Moreover, the results from the genome-wide off-target assessments, compared with other off-target s

48 ccine target with minimal risk of generating off-target autoimmunity.

49 First, we greatly reduce off-target base editing by installing mutations into our

50 on and broaden the toolkit for investigating off-target binding behavior.

51 uman nNOS potency and selectivity and reduce off-target binding by (a) truncating the original scaffo

52 serum and excellent specificity with minimal off-target binding even to closely related proteins such

53 Using the model, we predict Cas9 off-target binding frequencies across the lambdaphage an

54 th affinity for the same site, demonstrating off-target binding in vivo that could not have been anti

55 cal ("color") coding because the strength of off-target binding is strongly sublinear in binding-site

56 Off-target binding may contribute to disease profiles of

57 However, background-from off-target binding of FISH probes and cellular autofluor

58 We identified off-target binding of FISH probes to cellular components

59 This raises questions about the possible off-target binding of this tracer to non-tau molecules a

60 ic categories) may suggest either additional off-target binding or a second binding site with differe

61 crystal structure, we also predict potential off-target binding that we experimentally confirm.

62 cells in the basal ganglia, indicating that off-target binding to neuromelanin is an insufficient ex

63 -containing neurons in the substantia nigra (off-target binding).

64 nd later rearranged the scaffold to decrease off-target binding.

65 maximize target engagement while minimizing off-target binding.

66 ents with higher specific affinity and lower off-target binding.

67 of distinct components inevitably increases off-target binding.

68 ain significant levels of recently proposed 'off target' binding sites for [(18)F]AV-1451, such as ne

69 toxicity issues that are caused by different off-target bindings.

70 s and consider how genetic variation affects off-target candidates for these loci.

71 l the examined samples were not detected any off-target-caused mutation events.

72 roughput screening of compound libraries for off-target cereblon interactions but also can guide lead

73 oth Cpf1 nucleases, we were unable to detect off-target cleavage for more than half of 20 different c

74 1.1)) variants exhibit substantially reduced off-target cleavage in human cells, but the mechanism of

75 driving mechanism and an explanation for RAG off-target cleavage observed in humans.

76 orporated through the Cas9 nuclease mediated off-target cleavage.

77 fficiently verifies substrate and suppresses off-target cleavage.

78 ns preserved Caco-2 permeability and reduced off-target CNS binding.

79 arget concentration, and a set of undesired "off-target" complexes, each with vanishing target concen

80 chemorepellant, critical for the removal of off-target contacts.SIGNIFICANCE STATEMENT To address th

81 ty to single mismatches and the reduction of off-target cutting using truncated guides.

82 Using this toxicity as a proxy to measure off-target cutting, we demonstrate with tens of thousand

83 earch dynamics is strongly influenced by the off-target cutting.

84 effect reported for the latter may be due to off-target cytotoxic effects.

85 s and axon regeneration, without substantial off-target damage.

86 However, off-target deaminations were detected more than 150 bp a

87 esthesia; microinjection as little as 0.5 mm off-target did not.

88 We furthermore present an siRNA off-target discovery pipeline that not only predicts the

89 However, the off-target diversion of yttrium-90 microspheres to tissu

90 el for the biophysical constraints governing off-target DNA binding.

91 ZF structures in minimizing the formation of off-target DNA complexes.

92 ation and minimize the unintended effects of off-target DNA methylation.

93 f protein binding and nuclease activation at off-target DNA sequences remains elusive.

94 roduplex formation induce rapid rejection of off-target DNA.

95 n targets and investigated activities at two off-targets: dopamine receptor subtype D2 and endocannab

96 These results also reveal the role of off-target drug effects on tumor microenvironment and de

97 useful to explore the clinical relevance of off-target drug effects.

98 Off-target edits could be eliminated by reducing the amo

99 Numerous off-target edits were identified in the targeted mRNA, b

100 loss of righting but this was also due to an off-target effect since it was present in Prkce(-/-) mic

101 h transiently impaired locomotion through an off-target effect that did not interfere with their abil

102 The off-target effect was evaluated by sequencing two putati

103 critical survival genes in a unique form of off-target effect we call DISE (death induced by surviva

104 treatment of cancer, but it interferes as an off-target effect with microtubule polymerization.

105 hin irradiated cancer cells, but also as an "off-target effect" depending on the interaction between

106 ized for both high on-target potency and low off-target effect.

107 ivery to overcome nonspecific adsorption and off-target effect.

108 coring function to evaluate the potential of off-target effect.

109 er cells, either as an "on-target" or as on "off-target" effect.

110 P catalytic inhibitors is challenging due to off-target effects and cellular toxicity.

111 lude that CRISPRc and CRISPRi have different off-target effects and combining these approaches provid

112 Genetic studies can also examine off-target effects and furnish causal inference.

113 that FA-CS-UA-NPs could effectively diminish off-target effects and increase local drug concentration

114 ibs) are characterized by multiple molecular off-target effects and increased coronary artery disease

115 Off-target effects and mosaicism are major concerns for

116 editing with tight temporal control, minimal off-target effects and multiplex targeting.

117 To limit off-target effects and serious mechanism-based toxicity,

118 g in rhesus monkey zygotes, with no detected off-target effects at selected off-target loci.

119 CEREP ExpresS profiling identified off-target effects at the cholecystokinin, dopamine D2,

120 cing of HIV-1 eradicated cells ruled out any off-target effects by our CRISPR/Cas9 technology that mi

121 Newly developed targeted therapy can exert off-target effects causing hypertension, thromboembolism

122 surrogates for clinical outcomes or whether off-target effects disrupt the association between the s

123 onsiderations for how to evaluate and reduce off-target effects for research and therapeutic applicat

124 n with high sensitivity and specificity, but off-target effects have been reported for CRISPR guide R

125 d a protein is a key component in minimizing off-target effects in drug discovery.

126 n the context of trauma and infection, their off-target effects in the context of tumor are variable.

127 despite its critical immunological roles and off-target effects in tumorigenesis.

128 We did not detect any off-target effects in two genome regions homologous to t

129 Of interest, we occasionally observed off-target effects induced by the 17nt but not the 20nt

130 We show that mitigating off-target effects is feasible in these datasets via com

131 Sensitive detection of off-target effects is important for translating CRISPR-C

132 , experiments with Btk-null B cells revealed off-target effects of ibrutinib on BCR signaling.

133 elative ease, but the on-target activity and off-target effects of individual sgRNAs can vary widely.

134 used MELK inhibitor OTSSP167, and potential off-target effects of MELK-targeting short hairpins.

135 ll lines revealed that microRNA (miRNA)-like off-target effects of RNAi are far stronger and more per

136 nalytical framework that segregates on- from off-target effects of RNAi.

137 In this regard, we have examined whether the off-target effects of the Food and Drug Administration (

138 hanisms remain elusive, ticagrelor may exert off-target effects through adenosine-related mechanisms.

139 hat maximize on-target activity and minimize off-target effects to enable more effective and efficien

140 n the nanomolar range, also demonstrating no off-target effects toward the other tested Zn(2+)-depend

141 No off-target effects were detected.

142 -resistant strains, lack of cytotoxicity and off-target effects, and excellent in vivo pharmacokineti

143 ficiently knockdown RNAs, but it is prone to off-target effects, and visualizing RNAs typically relie

144 man embryos with negligible mosaicism and no off-target effects, bringing this editing tool closer to

145 Off-target effects, drug-drug interactions, and emerging

146 cyclophilin paralogs and exhibit significant off-target effects, immunosuppression, and toxicity.

147 o via their known receptors, with negligible off-target effects, to induce protective immunity.

148 ly assess the prevalence and consequences of off-target effects.

149 exchange leading to bispecific antibody and off-target effects.

150 t depend on both on-target and immunological off-target effects.

151 rocesses and the manner by which they reduce off-target effects.

152 The A2bR agonist BAY 60-6583 showed off-target effects.

153 pacity of damaged nerves without deleterious off-target effects.

154 family kinases, which may lead to unintended off-target effects.

155 eans to interrogate targets while minimizing off-target effects.

156 mise to improve drug specificity by reducing off-target effects.

157 y while exhibiting virtually no anaphylactic off-target effects.

158 immune, epithelial, or neural cells without off-target effects.

159 in-vitro antiviral activity while minimising off-target effects.

160 powerful genome editing technology, yet with off-target effects.

161 r mechano-gated channels and exerts multiple off-target effects.

162 JNK inhibition with SP600125 shows off-target effects.

163 g, germ-line transmission and for minimizing off-target effects.

164 ited for designing an inhibitor with minimal off-target effects.

165 vity patterns and the prediction of possible off-target effects.

166 t knockdown of disease symptoms, and limited off-target effects.

167 ription inhibition, and the ability to avoid off-target effects.

168 nology is far less susceptible to systematic off-target effects.

169 treatment resistance, and cause problematic off-target effects.

170 te distinct signalling pathways and to cause off-target effects.

171 te heterogeneous small RNAs with undesirable off-target effects.

172 s or to balance editing efficiency and toxic/off-target effects.

173 cilitate design of therapeutics with reduced off-target effects.

174 esults contribute to better interpreting the off-target efficacy of TKIs in tumors and to envisaging

175 Methods for preventing off-target embolization, increasing the specificity of m

176 pathways can potentiate the establishment of off-target epialleles.

177 ences, SpCas9-HF1 rendered all or nearly all off-target events undetectable by genome-wide break capt

178 ion in countering the deleterious effects of off-target excitation.

179 design are mainly concerned with predicting off-targets for a given sgRNA using basic sequence featu

180 Ai construct was prepared from the conserved off-target free partial HaCHI gene sequence and was used

181 more efficiently and cleanly, and with less off-target genome modification, than a current Cas9 nucl

182 lationships in binding to COMT and the novel off-target HIBCH.

183 by limiting their capability for large-scale off-target identification.

184 city, as measured by the abscopal effect (an off-target immune response).

185 good arguments in favor of suppressing such "off-target" immune responses.

186 Taken together, our findings designate off-target inhibition of CatD as a principal driver of o

187 that this pipeline accurately predicts siRNA off-target interactions and enables off-targeting potent

188 The off-target interactions can be responsible for either th

189 No off-target interactions were detected for 1 in a wide pa

190 age the desired kinase while avoiding myriad off-target kinases.

191 e that human genetic variation can alter the off-target landscape genome-wide including creating and

192 An unbiased screen for off-target lesions using a novel set of CCR5-targeting n

193 h no detected off-target effects at selected off-target loci.

194 5-HT7R while having no relevant affinity for off-target M1R and hERG channel.

195 at this drug blocks cell division through an off-target mechanism.

196 d to largely mutually exclusive on-target or off-target mechanisms in which tumors either retain depe

197 pression of enzymes can result in unintended off-target metabolism arising from enzyme promiscuity.

198 homology to the target site, thus unintended off-targets might additionally be cleaved.

199 ach is that corrected iPSCs that are free of off-target modifications can be identified before differ

200 in, and lead to the accumulation of numerous off-target modifications.

201 a during the exploration of both correct and off-target muscle fibers in Drosophila embryos.

202 Motoneuron filopodia repeatedly contacted off-target muscle fibers over several hours during late

203 emonstrate that filopodia repeatedly contact off-target muscles over several hours, until they ultima

204 ion of multiple loci, without any observable off-target mutagenesis and prior modification of the hos

205 tly obtain genome-edited clones with minimal off-target mutagenesis and with indel mutation frequenci

206 ortantly, CIRCLE-seq can be used to identify off-target mutations associated with cell-type-specific

207 oncentrations showed a higher propensity for off-target mutations in cells.

208 hole genome sequencing revealed little to no off-target mutations in these strains.

209 a highly precise tool, as we did not detect off-target mutations in Tomelo.

210 rehensive method for identifying genome-wide off-target mutations of CRISPR-Cas9.

211 ed mutagenesis and the adverse generation of off-target mutations vary greatly between different orga

212 ches for identifying CRISPR-Cas9 genome-wide off-target mutations.

213 he wild-type MYBPC3 gene without evidence of off-target mutations.

214 in AID activity at the Ig switch region and off-target Myc gene.

215 Potential new strategies to overcome off-target nanomaterial accumulation may involve manipul

216 mmunization strategies that seek to minimize off-target non-NAb responses.

217 y determinant of podocyte injury and a known off target of the anti-CD20 antibody rituximab (RTX).

218 currently mutated in B cell lymphomas, is an off-target of the normal somatic hypermutation process t

219 olase (HIBCH) as a possible toxicity-causing off-target of tolcapone, and this protein is not bound b

220 action screens in a kidney panel revealed no off-targets of concern.

221 lant disease, expanding the search space for off-targets of custom TAL effectors, and highlighting th

222 Thus, identifying the genome-wide off-targets of lead compounds or existing drugs will be

223 udy the cellular selectivity and the on- and off-targets of Targapremir-210.

224 In vitro biochemical methods for finding off-targets offer the potential advantages of greater re

225 ning resolution and analyzing the effects of off targets on hit calling.

226 tibody functions, while minimizing potential off-target oncogenic events.

227 activation of a cellular immune response, or off-target organ damage by BNP116.I-1c gene therapy in p

228 ural killer (NK) cells, reducing the risk of off-target-organ toxicity.

229 article structure affects biodistribution to off-target organs.

230 ive transport and local irradiation to avoid off-target oxidation.

231 er, chemical inhibition by BEL is subject to off-target pharmacologic effects.

232 perties governing CNS exposure and undesired off-target pharmacology such as hERG interactions.

233 he need for new and improved drugs with less off-target pharmacology.

234 -neural ectoderm and otic lineage cells from off-target populations.

235 ts siRNA off-target interactions and enables off-targeting potential comparisons between different si

236 off-target transcripts but also computes the off-targeting potential of a given siRNA.

237 with retained BGT1 activity and an improved off-target profile compared to 5.

238 physicochemical properties, solubility, and off-target profile of 1, an inhibitor of TarO, an early

239 dCCMS) strategy to effectively differentiate off-target profiles.

240 STOPs, our resource includes annotations for off-target propensity, percentage of isoforms targeted,

241 apidly in cells, but ensuing time-dependent, off-target protein modification can erode selectivity an

242 k the ligands of interest to assess possible off-target proteins, human variants and pathway informat

243 to enhance target specificity while reducing off-target radiation dose to healthy tissue during paylo

244 mate that up to one out of 60 cells contains off-target RAG cleavage.

245 on, while thwarting more slowly accumulating off-target reactivity in cell and animal models.

246 auses of one hurdle to clinical development, off-target reactivity, or nonspecificity.

247 ics properties coupled with limited unwanted off-target reactivity.

248 eImp is whole-genome imputation based on the off-target reads from deep whole-exome sequencing.

249 here rapid metabolic degradation can lead to off-target responses.

250 nhibition of SPCA1a by Tg might represent an off-target risk.

251 We also demonstrate that the off-target RNA knockdown and hepatotoxicity is attenuate

252 toxicity can occur as a result of unintended off-target RNase H1 dependent RNA degradation.

253 off-target assessments, compared with other off-target scoring tools, indicate that the statistical

254 tudies of resistance selection should assess off-target selection for resistance (eg, within the micr

255 Moreover, we find dozens of RAG off-target sequences that are generated via RAG tracking

256 h in vivo concentrations bring potential for off-target side effects, and 3) there is a need to bind

257 ma concentrations by 90%, thereby decreasing off-target side-effects.

258 n and translocation frequency to IGH and AID off-target sites in human chronic lymphocytic leukaemia

259 Graphical visualization of on-target and off-target sites in the genome is provided for target va

260 gate how nucleosomes affect Cas9 cleavage at off-target sites in vitro, we used a single guide RNA (s

261 vity at on-target sites, but their impact at off-target sites is unknown.

262 The list of off-target sites showing activity in cells was influence

263 However, Cas9 can cleave off-target sites that are not fully complementary to the

264 ddition, this enzyme produces DNA lesions at off-target sites that lead to mutations and chromosome t

265 e populations of individuals, most candidate off-target sites will be rare, underscoring the need for

266 comprehensive biochemical identification of off-target sites with independent cell-based measurement

267 ese nucleases have also been shown to cut at off-target sites with mutagenic consequences.

268 by nuclease-induced toxicity at both on- and off-target sites, likely due to DNA damage.

269 in altered on-target sites and novel potent off-target sites, which can predispose patients to treat

270 ect was evaluated by sequencing two putative off-target sites, which have 3 and 1 mismatched nucleoti

271 ID nuclear residence increases DNA damage at off-target sites.

272 requency to the Igh locus and to several AID off-target sites.

273 he guide RNA sequences and predict potential off-target sites.

274 tendency to cleave DNA non-specifically at "off-target" sites.

275 y on NaV1.7 and 500-fold selectivity against off-target sodium channels.

276 ct brain time-activity curves, suggesting no off-target specific binding of the tracer in the healthy

277 t of human genetic variation on both on- and off-target specificity.

278 ed enhancement of anti-PD-L1 efficacy due to off-target suppression of the activity of tumor-infiltra

279 le radioactive accumulation (</= 0.1% ID) in off-target tissues after 72h.

280 an enhanced therapeutic effect with reduced off-target toxic side effects.

281 like pancreatic ductal adenocarcinoma, cause off-target toxicities in normal, healthy tissue, highlig

282 challenge for nanodrug delivery and causing off-target toxicities, using an FDA approved nutrition s

283 e of the target pathogen, thereby minimizing off-target toxicities.

284 psulation can improve targeting, provide low off-target toxicity and most importantly reduce FTY720-i

285 cer targets and evaluating the likelihood of off-target toxicity associated with these targets.

286 These compounds show no off-target toxicity in zebrafish embryos, do not cause h

287 Using our strategy, we predicted the off-target toxicity observed in past clinical trials.

288 d to improve efficacy and/or reduce possible off-target toxicity of TNFSF ligands for cancer immunoth

289 o imperfect selectivity that leads to either off-target toxicity or tumor resistance.

290 ability to increase drug solubility, reduce off-target toxicity, enhance blood circulation lifetime,

291 poietic and hematopoietic cells indicated no off-target toxicity.

292 lack selectivity and may be associated with off-target toxicity.

293 cells or antibody based therapy with minimal off-target toxicity.

294 to phagocytic cells, significantly reducing off-target toxicity.

295 ommonly suffer from poor tumor specificity, "off-target" toxicity, and limited clinical efficacy.

296 iscovery pipeline that not only predicts the off-target transcripts but also computes the off-targeti

297 well as surprisingly sensitive reporters of off-target transgene expression.

298 block key identified mediator(s) to suppress off-target tumorigenic effects of hepatic RFA.

299 CMV-specific and functional T cells, whereas off-target vaccine responses activating memory T cells f

300 m (ventMAP) to enable automated detection of off-target ventilation (OTV) delivery in critically-ill