2.50
Hdl Handle:
http://hdl.handle.net/10033/620030
Title:
Specific in vivo knockdown of protein function by intrabodies.
Authors:
Marschall, Andrea L J; Dübel, Stefan; Böldicke, Thomas
Abstract:
Intracellular antibodies (intrabodies) are recombinant antibody fragments that bind to target proteins expressed inside of the same living cell producing the antibodies. The molecules are commonly used to study the function of the target proteins (i.e., their antigens). The intrabody technology is an attractive alternative to the generation of gene-targeted knockout animals, and complements knockdown techniques such as RNAi, miRNA and small molecule inhibitors, by-passing various limitations and disadvantages of these methods. The advantages of intrabodies include very high specificity for the target, the possibility to knock down several protein isoforms by one intrabody and targeting of specific splice variants or even post-translational modifications. Different types of intrabodies must be designed to target proteins at different locations, typically either in the cytoplasm, in the nucleus or in the endoplasmic reticulum (ER). Most straightforward is the use of intrabodies retained in the ER (ER intrabodies) to knock down the function of proteins passing the ER, which disturbs the function of members of the membrane or plasma proteomes. More effort is needed to functionally knock down cytoplasmic or nuclear proteins because in this case antibodies need to provide an inhibitory effect and must be able to fold in the reducing milieu of the cytoplasm. In this review, we present a broad overview of intrabody technology, as well as applications both of ER and cytoplasmic intrabodies, which have yielded valuable insights in the biology of many targets relevant for drug development, including α-synuclein, TAU, BCR-ABL, ErbB-2, EGFR, HIV gp120, CCR5, IL-2, IL-6, β-amyloid protein and p75NTR. Strategies for the generation of intrabodies and various designs of their applications are also reviewed.
Affiliation:
Helmholtz Centre for infection researchz, Inhoffenstr. 7, 38124 Braunschweig.
Citation:
Specific in vivo knockdown of protein function by intrabodies. 2015, 7 (6):1010-35 MAbs
Journal:
mAbs
Issue Date:
2015
URI:
http://hdl.handle.net/10033/620030
DOI:
10.1080/19420862.2015.1076601
PubMed ID:
26252565
Type:
Article
Language:
en
ISSN:
1942-0870
Appears in Collections:
Publications of the RG Rekombinante Proteinexpression (RPEX)

Full metadata record

DC FieldValue Language
dc.contributor.authorMarschall, Andrea L Jen
dc.contributor.authorDübel, Stefanen
dc.contributor.authorBöldicke, Thomasen
dc.date.accessioned2016-09-09T14:04:03Z-
dc.date.available2016-09-09T14:04:03Z-
dc.date.issued2015-
dc.identifier.citationSpecific in vivo knockdown of protein function by intrabodies. 2015, 7 (6):1010-35 MAbsen
dc.identifier.issn1942-0870-
dc.identifier.pmid26252565-
dc.identifier.doi10.1080/19420862.2015.1076601-
dc.identifier.urihttp://hdl.handle.net/10033/620030-
dc.description.abstractIntracellular antibodies (intrabodies) are recombinant antibody fragments that bind to target proteins expressed inside of the same living cell producing the antibodies. The molecules are commonly used to study the function of the target proteins (i.e., their antigens). The intrabody technology is an attractive alternative to the generation of gene-targeted knockout animals, and complements knockdown techniques such as RNAi, miRNA and small molecule inhibitors, by-passing various limitations and disadvantages of these methods. The advantages of intrabodies include very high specificity for the target, the possibility to knock down several protein isoforms by one intrabody and targeting of specific splice variants or even post-translational modifications. Different types of intrabodies must be designed to target proteins at different locations, typically either in the cytoplasm, in the nucleus or in the endoplasmic reticulum (ER). Most straightforward is the use of intrabodies retained in the ER (ER intrabodies) to knock down the function of proteins passing the ER, which disturbs the function of members of the membrane or plasma proteomes. More effort is needed to functionally knock down cytoplasmic or nuclear proteins because in this case antibodies need to provide an inhibitory effect and must be able to fold in the reducing milieu of the cytoplasm. In this review, we present a broad overview of intrabody technology, as well as applications both of ER and cytoplasmic intrabodies, which have yielded valuable insights in the biology of many targets relevant for drug development, including α-synuclein, TAU, BCR-ABL, ErbB-2, EGFR, HIV gp120, CCR5, IL-2, IL-6, β-amyloid protein and p75NTR. Strategies for the generation of intrabodies and various designs of their applications are also reviewed.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimalsen
dc.subject.meshAntibodiesen
dc.subject.meshCell Nucleusen
dc.subject.meshCytoplasmen
dc.subject.meshEndoplasmic Reticulumen
dc.subject.meshGene Knockdown Techniquesen
dc.subject.meshHumansen
dc.subject.meshIntracellular Spaceen
dc.subject.meshModels, Immunologicalen
dc.subject.meshProteomeen
dc.titleSpecific in vivo knockdown of protein function by intrabodies.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection researchz, Inhoffenstr. 7, 38124 Braunschweig.en
dc.identifier.journalmAbsen

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