title: Selection and characterization of llama single domain antibodies against N-terminal huntingtin.
abstract: Huntington disease is caused by expansion of a CAG repeat in the huntingtin gene that is translated into an elongated polyglutamine stretch within the N-terminal domain of the huntingtin protein. The mutation is thought to introduce a gain-of-toxic function in the mutant huntingtin protein, and blocking this toxicity by antibody binding could alleviate Huntington disease pathology. Llama single domain antibodies (VHH) directed against mutant huntingtin are interesting candidates as therapeutic agents or research tools in Huntington disease because of their small size, high thermostability, low cost of production, possibility of intracellular expression, and potency of blood-brain barrier passage. We have selected VHH from llama phage display libraries that specifically target the N-terminal domain of the huntingtin protein. Our VHH are capable of binding wild-type and mutant human huntingtin under native and denatured conditions and can be used in Huntington disease studies as a novel antibody that is easy to produce and manipulate.
authors.affiliation: Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
authors.forename: Menno H
authors.initials: MH
authors.lastname: Schut
authors.forename: Barry A
authors.initials: BA
authors.lastname: Pepers
authors.forename: Rinse
authors.initials: R
authors.lastname: Klooster
authors.forename: Silvère M
authors.initials: SM
authors.lastname: van der Maarel
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Khatabi
authors.forename: Theo
authors.initials: T
authors.lastname: Verrips
authors.forename: Johan T
authors.initials: JT
authors.lastname: den Dunnen
authors.forename: Gert-Jan B
authors.initials: GJ
authors.lastname: van Ommen
authors.forename: Willeke M C
authors.initials: WM
authors.lastname: van Roon-Mom
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000918:Antibody Specificity; D000939:Epitopes / Q000276:immunology; D004926:Escherichia coli; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000276:immunology / Q000628:therapy*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000276:immunology*; D011485:Protein Binding
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins