ライフサイエンスコーパス: intrabody

1 when expressed as intracellular antibodies ("intrabodies").

2 specific, anti-Htt intracellular antibodies (intrabodies).

3 e initial panel of intracellular antibodies (intrabodies).

4 gregates, compared with controls lacking the intrabody.

5 on of mutant huntingtin, a process slowed by intrabody.

6 ntracellularly in dopaminergic neurons as an intrabody.

7 ression vectors and expressed as cytoplasmic intrabodies.

8 v fragments must fulfill to act as efficient intrabodies.

9 ncrease the likelihood of finding functional intrabodies.

10 One anti-apoptotic intrabody, intrabody 5 (IB5), recognized pyruvate kinase M2 (PKM2),

11 ngton's disease (HD), we show that Hsp70 and intrabody actually affect different aspects of the disea

12 ble approach to the development of effective intrabodies against other intracellular targets.

13 Intracellular antibodies (intrabodies) against htt have been shown to reduce htt a

14 The optogenetically-enhanced intrabodies allow fast and reversible regulation of both

15 Functionalization of intrabodies allowed specific protein knockdown in living

16 kappa B inhibitors alone or the anti-Tat sFv intrabodies alone.

17 The scFv4B12 intrabody also increased the secretion of Z alpha1-antit

18 Screening of intrabodies and E3 ligases for optimal BioPROTAC constru

19 ge display for effective and specific use as intrabodies and immunolabels in mammalian cells includin

20 nificantly more potent than earlier anti-htt intrabodies and is a potential candidate for gene therap

21 ctively targeting betaarr interactions using intrabodies and provide a novel framework for fine-tunin

22 n addition, the combined use of anti-Tat sFv intrabodies and the two NF-kappa B inhibitors retained t

23 mera (BioPROTAC) composed of a SOD1-specific intrabody and an E3 ubiquitin ligase.

24 ar single-chain variable fragments (scFvs) ("intrabodies") and selected for those rescuing cells from

25 Intracellular antibodies (intrabodies) and the chaperone, heat shock protein 70 (H

26 such as soluble Tie-2 receptors, anti-Tie-2 intrabodies, anti-Ang-2 antibodies, and peptide-Fc conju

27 ceptor and/or ligand-competitive antibodies, intrabodies, antisense ribonucleotides, ribozymes, phosp

28 Here, we describe a novel intrabody approach to examine the role of these enzymes

29 lude from this investigation that engineered intrabodies are a potential new class of therapeutic age

30 Intrabodies are engineered single-chain antibodies in wh

31 Intrabodies are expressed inside cells and directed to d

32 Intrabodies are normally single chain Fv fragments compr

33 10Fn3 intrabodies are well expressed in mammalian cells and ar

34 Although intracellular antibodies (intrabodies) are being explored as putative therapeutic

35 findings strongly implicate nanobody-derived intrabodies as novel tools to study GPCR biology.

36 his article, we review studies of the use of intrabodies as research tools and therapeutic agents aga

37 These findings establish intrabodies as versatile tools for dissecting the confor

38 to test the use of intracellular antibodies (intrabodies) as a means of blocking the pathogenesis of

39 tibodies that are expressed intracellularly (intrabodies) as genetically encoded tools to control ion

40 gged with photoconvertible mEos expressed as intrabodies, as a proof-of-concept to perform single-par

41 The affinities of these intrabodies, as measured by surface plasmon resonance, v

42 We find that the PRR-binding intrabodies, as well as V(L)12.3, which binds the N-term

43 All sFvs could be expressed as intrabodies at high levels in transiently transfected 29

44 It also distinguishes intrabodies based on their functional effects and chaper

45 onstrate the potential for development of an intrabody-based strategy to block angiogenesis and preve

46 eptor-tyrosine kinases, we developed a novel intrabody-based strategy.

47 is for polyQ toxicity and the development of intrabody-based therapeutics for HD.

48 polyP domains, and Happ1 and Happ3, two new intrabodies, bind the unique, P-rich epitope located bet

49 that compromising this pathogenic epitope by intrabody binding represents a novel therapeutic strateg

50 We also note that intrabody binding represents a powerful tool for determi

51 nhibits ligand-induced signaling, the VUN103 intrabody blocks constitutive signaling, indicating the

52 ntages, in particular the ability to isolate intrabodies by direct genetic selection, which obviates

53 ure models of HD, anti-N-terminal huntingtin intrabodies (C4 sFv) reduce aggregation and cellular tox

54 ovide proof-in-principle that anti-hCyclinT1 intrabodies can be designed to block HIV-1 replication w

55 Intracellular antibodies (intrabodies) can bind to specific targets in cells but i

56 In this study, we worked to develop intrabodies capable of binding specific proteoforms.

57 Recently, we have reported a novel intrabody (chromobody)-based approach to study the spati

58 trabodies mirrored that of betaarr1, and the intrabodies co-localized with betaarr1 at the cell surfa

59 Both of these intrabodies colocalize with H-Ras, K-Ras, and G12V mutan

60 ding properties of intracellular antibodies (intrabodies), combined with their ability to be stably e

61 This paper demonstrates a high data-rate intrabody communication link based on Lithium Niobate (L

62 nd delayed cellular intoxication, whereas E3 intrabody completely blocked the cytopathic effects of T

63 format, based on a previously characterised intrabody consensus scaffold, to generate diverse intrab

64 nformational specificity was preserved after intrabody conversion as demonstrated by the ability for

65 We hypothesized that an intrabody could bind newly synthesized KDR and block rec

66 This intrabody decreases the cytotoxicity of mutant huntingti

67 rgeted single-chain antibody fragment (scFv) intrabodies demonstrated that the intradiabody is signif

68 lication of intracellular acting antibodies (intrabodies), derived from the variable domain of cameli

69 contrast, human Tie-2-monospecific pAd-1S05 intrabody did not affect the growth of tumors, indicatin

70 ess this issue, we generated a panel of five intrabodies, directed against catalytically inactive mur

71 Tagging iPSD scaffold gephyrin with a PSD-95 intrabody (dissociation constant ~4 nM) leads to mistarg

72 We therefore explored enhancing intrabody efficacy via fusions to heterologous functiona

73 This CCR5-intrabody efficiently blocked surface expression of huma

74 assays and were often found to be functional intrabodies, enabling tracking or inhibition of endogeno

75 on-sensor scFvs as intracellular antibodies (intrabodies) enhanced insulin-induced tyrosyl phosphoryl

76 Intrabody-expressing cells were shown to be highly refra

77 However, high levels of intrabody expression have been required to obtain even l

78 Ad-HAK infection resulted in intrabody expression in >90% of human umbilical vein end

79 in the nucleus through spatially programmed intrabody expression.

80 Bispecific intrabody FAP1V2 fused with antibody V(H) regions, was s

81 on of cells expressing chimeric GPCRs, these intrabodies first translocate to the cell surface, follo

82 n PSD-95 function, we validated their use as intrabody fluorescent probes.

83 truct single-chain intracellular antibodies (intrabodies) for expression in the cytoplasm and the nuc

84 We adapted these FABs to an intrabody format by converting them to single-chain vari

85 ve identified a highly effective ER-targeted intrabody format for the simultaneous functional knockou

86 at the consensus scaffolds are functional as intrabody fragments without an intra-domain disulfide bo

87 tion that is often not predictive of in vivo intrabody function and provide a more efficient use of l

88 ld is a robust framework by which to improve intrabody function.

89 n the absence of a disulfide bond to improve intrabody function.

90 t antibody-like proteins, termed Fibronectin intrabodies generated with mRNA display (FingRs), that b

91 Previous studies with intrabodies had demonstrated that the Tie-2 receptor pat

92 The effects of intrabodies have been investigated using structural, reg

93 Intrabodies have been used to specifically target intrac

94 These intrabodies have demonstrated their versatility by contr

95 The PRR-binding intrabodies have no effect on Htt localization, but they

96 Recently, intrabodies have shown promising antiaggregation and neu

97 sing both HLA I RNA interference (siRNA) and intrabody (IB) technology.

98 single-chain variable fragments (scFvs) and intrabodies (iBs) from the phosphorylated tau-specific a

99 in in vivo when expressed intracellularly as intrabodies in dopaminergic neurons.

100 in vitro and allows for direct selection of intrabodies in vivo.

101 Cytoplasmic expression of 7F intrabody in Vero cells inhibited TcdB autoprocessing an

102 The expression of intracellular antibodies (intrabodies) in eukaryotic cells has provided a powerful

103 One anti-apoptotic intrabody, intrabody 5 (IB5), recognized pyruvate kinase

104 Fusion of the mODC-PEST motif to intrabodies is a valuable general approach to specifical

105 o specific targets in cells but isolation of intrabodies is currently difficult.

106 A challenge in the isolation of effective intrabodies is the ability to find molecules that exhibi

107 The DO-1 intrabody is a useful tool to study those functions of p

108 athrin interaction, and when expressed as an intrabody, it robustly inhibited agonist-induced endocyt

109 The remaining intrabody levels were amply sufficient to target N-termi

110 paper, we describe the de novo synthesis of intrabody libraries based on the IAC consensus sequence.

111 Completely de novo intrabody libraries can be rapidly generated in vitro by

112 body consensus scaffold, to generate diverse intrabody libraries for direct in vivo screening.

113 were identified which can form the basis of intrabody libraries for direct screening.

114 n example, a single immunoglobulin VH domain intrabody library was screened directly in yeast with an

115 est that large interfering molecules such as intrabodies may be useful inhibitors of viral protein-pr

116 Intrabodies may therefore be a useful gene-therapy appro

117 Here, we present the crucial experiment of intrabody-mediated in vivo suppression of neuropathology

118 This study suggests that intrabody-mediated modulation of abnormal neuronal prote

119 The translocation pattern of intrabodies mirrored that of betaarr1, and the intrabodi

120 P-rich region (PRR) of HDx-1 are defined by intrabodies: MW7 binds the two polyP domains, and Happ1

121 able cell line expressing the most effective intrabody, NAC32, showed highly significant reductions i

122 This approach to intrabodies obviates the need for phage antibody librari

123 Abeta(1-42)-specific intracellular antibody (intrabody), oligodendrocyte and myelin marker expression

124 binding domain with a single-chain Fv (scFv) intrabody or a fibronectin type III domain monobody that

125 binant single-chain antibody fragment rabbit intrabody (pAd-2S03) capable of inhibition of both mouse

126 This initial intrabody pattern of CFU-S distribution in murine embryo

127 of the biological activity of the anti-TES1 intrabody pools demonstrated that they were all able to

128 sFvs into discrete or minimally overlapping intrabody pools.

129 ce of disulfide bond-independent binding for intrabody potency suggests a generally applicable approa

130 cts, the proteasomal degradation of the scFv intrabody proteins themselves was reduced<25% by the add

131 Intracellular antibodies (intrabodies) provide an attractive means for manipulatin

132 onstrate that the intrinsic stability of the intrabody, rather than its affinity for the antigen, dic

133 Intracellular antibodies (intrabodies) recognise and bind to proteins in cells and

134 We previously showed that V(L)12.3, an intrabody recognizing the N terminus of Htt, and Happ1,

135 gnizing the N terminus of Htt, and Happ1, an intrabody recognizing the proline-rich domain of Htt, bo

136 TDP-43 RRM1 intrabodies reduce WT SOD1 misfolding in human cell cult

137 tum of HD mice via adenoviral infection, the intrabody reduces neuropil aggregate formation and ameli

138 These findings suggest that the intrabody reduces the specific neurotoxicity of cytoplas

139 Intracellular antibodies (intrabodies) represent a new class of neutralizing molec

140 o-associated virus mediated delivery of this intrabody results in improvement of cardiac performance

141 This direct phage to intrabody screening (DPIS) strategy should allow investi

142 Here, we adapted this assay to develop intrabody selection after Tat export (ISELATE), a high-t

143 While the Nb7 intrabody selectively inhibits ligand-induced signaling,

144 Interestingly, we discovered that intrabody sensors can also report betaarr1 recruitment a

145 Our characterization of intrabody sensors for betaarr1 recruitment and trafficki

146 Growing number of intrabodies should make their incorporation into optogen

147 The intrabody significantly inhibited growth of both tumors

148 Plasmid-mediated expression of the tethered intrabody significantly reduced KDR expression (from 82.

149 from the cytosol to the nucleus, mediated by intrabodies tagged with an SV40 nuclear localization sig

150 ly, formation of iPSD condensates forces the intrabody-tagged gephyrin out of ePSD condensates.

151 against Ras with mRNA display resulted in an intrabody (termed RasIn1) that binds with a KD of 2.1muM

152 Seven of the selected intrabodies tested do not perturb cellular function when

153 e libraries already in existence to identify intrabodies that are active in vivo.

154 le-chain Fv antibodies (scFvs), expressed as intrabodies that bind htt and prevent aggregation, show

155 framework for development of nanobodies and intrabodies that target proteoforms.

156 Significantly, a single-domain intrabody that is functionally expressable in the cytopl

157 gineered synthetic intracellular antibodies (intrabodies) that are capable of modulating mTOR signali

158 expressed single-chain Fv (sFv) antibodies (intrabodies) that bind with unique HD protein epitopes.

159 n genetically encoded antibody-like ligands (intrabodies) that recognize active, GTP-bound K- and H-R

160 In the presence of the C4 sFv intrabody, the proportion of HD flies surviving to adult

161 Moreover, when expressed as "intrabodies," these V(H)Hs rendered cells resistant to r

162 When expressed as intrabodies, they inhibited G protein activation (cyclic

163 d Akt phosphorylation by genetically encoded intrabodies, thus supporting a mechanism of inhibition a

164 h may find application in the development of intrabodies to a wide variety of intracellular targets.

165 uses include as intracellular antibodies or intrabodies to bind and deliver cargo to specific protei

166 Our strategy for generating intrabodies to investigate cardiac disease combined with

167 We engineer optically-controlled intrabodies to regulate genomically expressed protein ta

168 The ability of the single-domain intrabody to inhibit huntingtin aggregation, which has b

169 s the plasma membrane targeted single domain intrabody to inhibit signalling by mutant RAS.

170 ansiently expressed them intracellularly as "intrabodies" to test their effects on beta2AR-dependent

171 osion and prolonged adult life compared with intrabody treatment alone.

172 election resulted in eight independent 10Fn3 intrabodies, two that require the N-terminal domain for

173 ce to use sFv-phage libraries as a source of intrabodies unless a pre-selection step to identify thes

174 e IDab format is therefore ideal for in vivo intrabody use.

175 Furthermore, the engineered intrabody variable light-chain (V(L))12.3, rescued toxic

176 Here, we design an intrabody version of a betaarr-recognizing nanobody (nan

177 Specificity of the intrabodies was testified using Western blot, co-immunop

178 whereas the effect of the monospecific scFv intrabodies was weaker.

179 The intrabody was essential for these effects, as confirmed

180 A single-chain variable fragment (scFv) intrabody was generated based on the sequence of mAb4B12

181 Intrabody was more successful at suppressing neurodegene

182 This anti-huntingtin sFv intrabody was tested in a cellular model of the disease

183 Tat single-chain intracellular antibody (sFv intrabody) was employed to obtain cooperative inhibition

184 ng highly specific intracellular antibodies (intrabodies), we tested various epitopes for their roles

185 different mechanisms of action of these two intrabodies, we then tested both in the brains of five m

186 Using cytosolic NbALFA-mScarlet intrabody, we achieve compartment-specific detection of

187 al sequence similarity, only two of the five intrabodies were able to significantly accumulate intrac

188 These anti-p53 intrabodies were additionally modified by addition of a

189 The intrabodies were developed using gene cloning technology

190 s or directly expressed in living neurons as intrabodies, where they bind their epitopes in the endop

191 dy capture (IAC) technology to isolate human intrabodies which bind to the oncogenic RAS protein.

192 Finally, intrabodies which can bind to intracellular proteins and

193 Furthermore, we could convert an intrabody which does not bind RAS in mammalian cells int

194 We generated an intracellular antibody (intrabody) whose binding to a unique epitope of human hu

195 hetic VHH phage-display library, we identify intrabodies with high affinity and specificity for diffe

196 Coexpression of anti-huntingtin sFv intrabodies with the abnormal huntingtin-GFP fusion prot

197 ombines the specificity and orthogonality of intrabodies with the spatiotemporal precision of optogen

198 We conclude that a combinational approach of intrabody with enhanced Hsp70 expression is beneficial i

199 cells and tissue, efficiently identifies the intrabody with most desirable features.

200 Interaction of the intrabody with mutant huntingtin increases the ubiquitin

201 brary could be directly screened in pools as intrabodies without prior knowledge of their individual