NR ATUA
AU Miller,T.W.; Messer,A.
TI Intrabody applications in neurological disorders: progress and future prospects.
QU Molecular Therapy : The Journal of the American Society of Gene Therapy 2005 Sep; 12(3): 394-401
PT journal article; review
AB Single-chain Fv and single-domain antibodies retain the binding specificity of full-length antibodies, but they can be expressed as single genes in phage or yeast surface-display libraries, thus allowing efficient in vitro selection from a naive human repertoire. Selected genes can then be expressed intracellularly in mammalian cells as intrabodies, with the potential for alteration of the folding, interactions, modifications, or subcellular localization of their targets. These reagents have been developed as therapeutics against cancer and HIV. Since misfolded and accumulated intracellular proteins characterize a wide range of neurodegenerative disorders, they are also potentially useful intrabody targets. Here, we review the extension of intrabody technology to the nervous system, in which studies of Huntington's disease have been used to develop the approach, and anti-synuclein and -beta-amyloid strategies are in the early stages of development. Research on several other neurodegenerations, including Parkinson's, Alzheimer's, and prion diseases, provides support for the development of intrabodies directed against specific targets, or possibly against more common downstream targets, as novel therapeutics and as drug discovery tools.
ZR 104
MH Alzheimer Disease/immunology/therapy; Amyloid beta-Protein/chemistry; Animals; Antibodies/therapeutic use; Drug Design; Gene Therapy/methods; Humans; Huntington Disease/immunology/therapy; Immunoglobulin Fragments/chemistry; Mice; Nervous System Diseases/*immunology/*therapy; Prion Diseases/immunology/therapy; Protein Engineering; Protein Folding; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
AD Wadsworth Center, New York State Department of Health, and Department of Biomedical Sciences, University at Albany, Albany, NY 12201, USA
SP englisch
PO USA