Proprietary phage libraries
(Naïve, semi-synthetic):

Display technologies include phage display, yeast display, ribosome display and mammalian cell display.


We have created various bespoke naïve and semi-synthetic llama VHH libraries for use with the various display technologies, so as to be able to take advantage of the strengths of the various display technologies. We source valuable VHHs both from llama immunization approaches and from in vitro semi-synthetic approaches.

This dual capability enables us to identify VHHs against challenging, immune-tolerant targets. Furthermore, we affinity-mature VHHs where necessary, in order to optimize drug efficacy. Bespoke libraries of VHH clones are routinely created and interrogated for desirable characteristics, targeting both the CDR1/2/3 binding regions as well as framework regions that affect desirable characteristics.

Thus, 272BIO is fully equipped with state-of-the-art display technology and expertise best to engineer VHHs and take advantage of their unique structural characteristics.

Biotherapeutics graphic 1

Structure and binding characteristics of the VHH domain. The typical organisation of the VHH domain is represented using the structure of a VHH to carbazol (PDB 1U0Q). In framework (FR) 2 (dark grey), the amino acids shown in cyan [in this case Phe42, Glu49, Arg50, and Phe52 (IMGT numbering) represent the hallmark residues that substitute the critical amino acids of VHs that participate in the interaction with the light chain. CDRs 1, 2, abd 3 are coloured in pink, green and red respectively. The loop of FR 3 shown in blue (also known as CDR4) presents significant variability (higher than in VHs of conventional antibodies) and may interact with the antigen (41-43). Frequently, the CDR3 is long and bends over FR 2 shielding its hydrophobic residues and helping to mask Trp 18 (cyan-green), which is key for the interaction of VH with the VL chain. The structure of the long CDR3s, much more frequently in camels, may be stabilised by non-canonical disulfide.