**Author details**

In another study, a large library of recombinant VLRs was constructed to target lysozyme, β-gal, cholera toxin subunit B, R-phycoerythrin and B-trisaccharide antigens using yeast surface display technologies [36]. This high-throughput technology platform offers the potential of rapid identification and isolation of monoclonal VLRs that specifically bind to target antigens with affinities in the micromolar to nanomolar range [36]. Using such display methods, the specificity of selected VLR antibodies can recognize the target antigen with high binding affinity up to 100-fold compared to conventional mouse mAb [36]. These data indicate that the function of VLRs is comparable or perhaps better than that of mammalian IgG antibodies. Therefore, it is speculated that VLRs may be an alternative reagent for the future

The fields of antibody engineering have undergone major advancements in the past few decades. New surface display technologies, in particular phage display and yeast display, are powerful tools that could facilitate the isolation of new antibodies with high specificities for a broad range of targets. Due to their affinity, which often is similar to conventional antibodies and reliable production, recombinant antibodies are becoming increasingly important in the field of diagnosis and therapy for targeting a wide range of diseases such as cancer, inflammatory, autoimmune and viral diseases. In view of natural scaffold design, previous studies showed that the sdAbs repertoires derived from animals such as camelid VHHs, shark VNARs and lamprey VLRs contain several advantages over conventional antibodies. One of the unusual characteristics shared among the sdAbs is that they possess better penetration ability. This feature allows the sdAbs to effectively penetrate into antigen clefts (enzyme active sites, viral capsids and cell surface receptors) which are not easily recognized by the concave surfaces of CDR loops of complex conventional antibodies. To date, due to their ability to target both refractory antigens and immunosilent epitopes, the engineered antibody fragments coupled with latest screening technologies have extensively been used in positron emission tomography and high-sensitivity (nonradioactive, noninvasive) laser technologies for medical imaging. To sum up, it is believed that with rapid progress in antibody engineering technologies, sdAbs will become indispensable as clinical and research

The authors would like to acknowledge support from University of Queensland, QIMR Berghofer Medical Research Institute in Australia and Malaysian Government, including Malaysian Ministry of Higher Education the Higher Institutions Centre of Excellence Program (Grant no.: 311/CIPPM/4401005), RUI Grant no.: RU(1001/CIPPM/811296) and USM Short

development of therapeutic and diagnostic applications.

**6. Conclusion**

190 Antibody Engineering

reagents in the next decades.

**Acknowledgements**

Term (Grant no.: 304/CIPPM/6313191).

Chiuan Herng Leow<sup>1</sup> \*, Qin Cheng2,3, Katja Fischer2,4 and James McCarthy2,4

\*Address all correspondence to: herng.leow@usm.my

1 Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Penang, Malaysia

2 QIMR Berghofer Medical Research Institute, Brisbane, Australia

3 Australian Army Malaria Institute, Brisbane, Australia

4 University of Queensland, Brisbane, Australia
