A VL single-domain antibody library shows a high-propensity to yield non-aggregating binders

A synthetic human VL phage display library, created by the randomization of all complementarity-determining regions (CDRs) in a VL scaffold, was panned against three test antigens to determine the propensity of the library to yield non-aggregating binders. A total of 22 binders were isolated against the test antigens and the majority (20) were monomeric. Thus, human VL repertoires provide an efficient source of non-aggregating binders and represent an attractive alternative to human VH repertoires, which are notorious for containing high proportions of aggregating species. Moreover, the solubility of VLs, in contrast to VHs, appears much less CDR dependent.