ライフサイエンスコーパス: intrabody

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

2 e initial panel of intracellular antibodies (intrabodies).

3 gregates, compared with controls lacking the intrabody.

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

5 ntracellularly in dopaminergic neurons as an intrabody.

6 v fragments must fulfill to act as efficient intrabodies.

7 ncrease the likelihood of finding functional intrabodies.

8 ression vectors and expressed as cytoplasmic intrabodies.

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

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

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

12 Functionalization of intrabodies allowed specific protein knockdown in living

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

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

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

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

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

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

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

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

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

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

23 Intrabodies are engineered single-chain antibodies in wh

24 Intrabodies are expressed inside cells and directed to d

25 Intrabodies are normally single chain Fv fragments compr

26 10Fn3 intrabodies are well expressed in mammalian cells and ar

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

51 This intrabody decreases the cytotoxicity of mutant huntingti

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

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

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

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

56 This CCR5-intrabody efficiently blocked surface expression of huma

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

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

59 Intrabody-expressing cells were shown to be highly refra

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

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

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

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

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

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

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

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

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

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

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

71 Intrabodies have been used to specifically target intrac

72 These intrabodies have demonstrated their versatility by contr

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

74 Recently, intrabodies have shown promising antiaggregation and neu

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

92 Intrabodies may therefore be a useful gene-therapy appro

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

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

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

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

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

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

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

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

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

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

103 sFvs into discrete or minimally overlapping intrabody pools.

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

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

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

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

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

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

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

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

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

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

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

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

116 The intrabody significantly inhibited growth of both tumors

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

138 The intrabody was essential for these effects, as confirmed

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

140 Intrabody was more successful at suppressing neurodegene

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

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

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

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

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

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

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

148 Finally, intrabodies which can bind to intracellular proteins and

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

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

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

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

153 Interaction of the intrabody with mutant huntingtin increases the ubiquitin

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