title: Discovery of novel candidate therapeutics and diagnostics based on engineered human antibody domains.
abstract: The smallest independently folded antibody fragments, the domains, are emerging as promising scaffolds for candidate therapeutics and diagnostics that bind specifically targets of interest. The discovery of such binders is based on several technologies including structure-based design and generation of libraries of mutants displayed on phage or yeast, next-generation sequencing for diversity analysis, panning and screening of the libraries, affinity maturation of selected binders, and their expression, purification, and characterization for specific binding, function, and aggregation propensity. In this review, we describe these technologies as applied for the generation of engineered antibody domains (eAds), especially those derived from the human immunoglobulin heavy chain variable region (VH) and the second domain of IgG1 heavy chain constant region (CH2) as potential candidate therapeutics and diagnostics, and discuss examples of eAds against HIV-1 and cancer-related proteins.
authors.forename: Weizao
authors.initials: W
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Gong
authors.forename: Tianlei
authors.initials: T
authors.lastname: Ying
authors.forename: Ponraj
authors.initials: P
authors.lastname: Prabakaran
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Zhu
authors.forename: Yang
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Miller Drive, Building 469, Room 150B, Frederick, MD 21702-1201, USA. chenw3@mail.nih.gov.
authors.forename: Dimiter S
authors.initials: DS
authors.lastname: Dimitrov
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000627:therapeutic use; D055808:Drug Discovery; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000627:therapeutic use; D015202:Protein Engineering; D017434:Protein Structure, Tertiary
chemical_list: D000906:Antibodies; D007135:Immunoglobulin Variable Region