Specific in vivo knockdown of protein function by intrabodies

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 a...

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Main Authors:	Marschall, Andrea LJ, Dübel, Stefan, Böldicke, Thomas
Format:	Online
Language:	English
Published:	Taylor & Francis 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966517/

id	pubmed-4966517
recordtype	oai_dc
spelling	pubmed-49665172016-08-24 Specific in vivo knockdown of protein function by intrabodies Marschall, Andrea LJ Dübel, Stefan Böldicke, Thomas Review 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. Taylor & Francis 2015-08-07 /pmc/articles/PMC4966517/ /pubmed/26252565 http://dx.doi.org/10.1080/19420862.2015.1076601 Text en © 2015 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Marschall, Andrea LJ Dübel, Stefan Böldicke, Thomas
spellingShingle	Marschall, Andrea LJ Dübel, Stefan Böldicke, Thomas Specific in vivo knockdown of protein function by intrabodies
author_facet	Marschall, Andrea LJ Dübel, Stefan Böldicke, Thomas
author_sort	Marschall, Andrea LJ
title	Specific in vivo knockdown of protein function by intrabodies
title_short	Specific in vivo knockdown of protein function by intrabodies
title_full	Specific in vivo knockdown of protein function by intrabodies
title_fullStr	Specific in vivo knockdown of protein function by intrabodies
title_full_unstemmed	Specific in vivo knockdown of protein function by intrabodies
title_sort	specific in vivo knockdown of protein function by intrabodies
description	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.
publisher	Taylor & Francis
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966517/
_version_	1613617790766284800

Specific in vivo knockdown of protein function by intrabodies

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