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

A synthetic human V-L phage display library, created by the randomization of all complementarity-determining regions (CDRs) in a V-L 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 V-L repertoires provide an efficient source of non-aggregating binders and represent an attractive alternative to human V-H repertoires, which are notorious for containing high proportions of aggregating species. Moreover, the solubility of V(L)s, in contrast to V(H)s, appears much less CDR dependent.