Blocking translocation of cell surface molecules from the ER to the cell surface by intracellular antibodies targeted to the ER
Open Access
- 1 January 2007
- journal article
- review article
- Published by Wiley in Journal of Cellular and Molecular Medicine
- Vol. 11 (1), 54-70
- https://doi.org/10.1111/j.1582-4934.2007.00002.x
Abstract
Intracellular antibodies (intrabodies) constitute a potent tool to neutralize the function of target proteins inside specific cell compartments (cytosol, nucleus, mitochondria and ER). The intrabody technology is an attractive alternative to the generation of gene-targeted knockout animals and complements or replaces knockdown techniques such as antisense-RNA, RNAi and RNA aptamers. This article focuses on intrabodies targeted to the ER. Intracellular anti-bodies expressed and retained inside the ER (ER intrabodies) are shown to be highly efficient in blocking the translocation of secreted and cell surface molecules from the ER to the cell surface. The advantage of ER intrabodies over cytoplasmic intrabodies is that they are correctly folded and easier to select. A particular advantage of the intrabody technology over existing ones is the possibility of inhibiting selectively post-translational modifications of proteins. The main applications of ER intrabodies so far have been (i) inactivation of oncogenic receptors and (ii) functional inhibition of virus envelope proteins and virus-receptor molecules on the surface of host cells. In cancer research, the number of in vivo mouse models for evaluation of the therapeutic potential of intrabodies is increasing. In the future, endosomal localized receptors involved in bacterial and viral infections, intracellular oncogenic receptors and enzymes involved in glycosylation of tumour antigens might be new targets for ER intrabodies.This publication has 109 references indexed in Scilit:
- Optimization and Functional Effects of Stable Short Hairpin RNA Expression in Primary Human Lymphocytes via Lentiviral VectorsMolecular Therapy, 2006
- Stable RNA interference of ErbB-2 gene synergistic with epirubicin suppresses breast cancer growth in vitro and in vivoBiochemical and Biophysical Research Communications, 2006
- Determinants of specific RNA interference-mediated silencing of human β-globin alleles differing by a single nucleotide polymorphismProceedings of the National Academy of Sciences of the United States of America, 2006
- KDEL-tagged anti-prion intrabodies impair PrP lysosomal degradation and inhibit scrapie infectivityBiochemical and Biophysical Research Communications, 2005
- The discovery of receptor tyrosine kinases: targets for cancer therapyNature Reviews Cancer, 2004
- Intradiabodies, Bispecific, Tetravalent Antibodies for the Simultaneous Functional Knockout of Two Cell Surface ReceptorsPublished by Elsevier BV ,2003
- Reversion of transformed phenotype in ovarian cancer cells by intracellular expression of anti folate receptor antibodiesGene Therapy, 2003
- Progress and problems with the use of viral vectors for gene therapyNature Reviews Genetics, 2003
- Intrabody-mediated phenotypic knockout of major histocompatibility complex class I expression in human and monkey cell lines and in primary human keratinocytesGene Therapy, 2002
- Expression and Functional Characterization of a Single Chain FV Antibody Directed against Secretions Involved in Plant Nematode Infection ProcessBiochemical and Biophysical Research Communications, 1996