Introduction 1 Fig. 1 a b VH VL shaded dark gray light gray CH CL hatched spheres  1964 1967 1989 2002 1 1993 1 1995 1997 2000a 2002 2003 2006 2006 2001 2006 Properties 1993 1994 1997 2000 1996 2001 1996 2004 2001 2005 2002 2001a 2004 2005a 2007 2000 2002 2001 1988 1994 2000 1997 2000 2000 1994 1996 1 Table 1 Advantages of camelid single-domain antibody fragments as compared to conventional antibody fragments Advantage Molecular basis Facile genetic manipulation Single-domain nature Increased functional size of immune libraries No decrease in library size because of reshuffling of VL and VH domains Facile production of multivalent formats More flexible linker design and no mispairing of VL and VH domains Facile production of oligoclonal preparations from single cells No mispairing of VL and VH domains High physicochemical stability Efficient refolding due to increased hydrophilicity and single-domain nature High solubility Increased hydrophilicity Recognition of hidden antigenic sites Small size and extended flexible CDR3 Rapid tissue penetration, fast clearance Small size Well expressed Efficient folding due to increased hydrophilicity and single-domain nature See text for references 2000 2005b 1 1990 1993 2006 2007 2002 1999 1999 2001 2001 2002 2002 1995 1996 2005 2003 1998 2006 2004 1996 2006 2003 2002 2001 2000 2003 2007 2007 2001 K D 2004 2006 2006 2002 2004 2006 2002 2005a Production in microorganisms Escherichia coli 2005 2006 E. coli E. coli 2005 E. coli 1997 2005 2005 2004 Saccharomyces cerevisiae 2000 2002 2002 Pichia pastoris 2006 2000 2005a 2006 2006 2000 2005b 2007 2000 E. coli 2002 E. coli 1995 2006 E. coli 1997 2000 2005b 2000b 2006 E. coli 2004 2007 2005 2007 P. pastoris 2006 1 2001b 2005a 2006 2007 2001b E. coli 2004 1 1997 2003 P. pastoris 2006 2006 Therapeutic applications 2005 2003 2004 2005 2 Table 2 Examples of therapeutic applications of camelid VHHs Disease Pathogen Target antigen VHH valency for disease target Additional fusion partner Reference Sleeping sickness Trypanosomes VSG oligomannose Monovalent Apolipoprotein L-I 2006 Infant diarrhea Rotavirus Unknown Monovalent None 2006 Infant diarrhea Rotavirus Unknown Monovalent Lactobacillus 2006 Piglet diarrhea E. coli F4 fimbriae Monovalent None 2006 Caries S. mutans I/II adhesion Monovalent None 2006 FMD FMD virus VP1 Monovalent PEG 2007 Sepsis N. meningitidis LPS Monovalent None 2006 Cancer – CEA Monovalent β-Lactamase 2004 Cancer – EGF receptor Bivalent Anti-albumin VHH 2007 Rheumatoid arthritis – TNFα Bivalent Anti-albumin VHH 2006 Brain disorders – α (2,3)-Sialoglycoprotein Monovalent None 2002 Neurodegenerative diseases – Bax Monovalent None 2006 2002 2003 E. coli 2005b 2006 2006 2006 2006 Streptococcus mutans 2006 2006 2007 2005a 2007 2007 2006 2004 2007 2007 2006 2006 2002 2006 2004 2006 2002 2006 2006 2006 Conclusions http://www.ablynx.com