EVOLUTIONARY MOLECULAR ENGINEERING

In the theory of evolution in nature, the number of inferior species, which are not compatible with the environment, are decreased naturally (natural selection). Around 1990, a new methodology, termed “combinatorial chemistry”, was developed in the science field. In this approach, molecular library (the mixture of various molecules) are prepared, and then, the ligand molecules with high-binding affinity to the target molecule are isolated from the library. The ligand molecules can be concentrated by the elimination of low-binding affinity molecules from the library, and it is termed “evolutionary molecular engineering” or “in vitro selection”.

Evolutionary molecular engineering and the separation technology termed “microbead-assisted capillary electrophoresis (MACE)”

MACE Separation, a technology that uses capillary electrophoresis, has been developed by Yoshimoto et al. at The University of Tokyo. It involves visualizing the screening stage of the evolutionary-engineering-type molecule-selection method, thus achieving high concentration rates for groups of binding molecules (this is almost the same as efficient natural selection). Yoshimoto et al. combined MACE Separation with the nucleic acid aptamer selection assay (SELEX) system, which is an evolutionary-engineering-type molecule-selection method, and in three rounds they identified 10 sequences, as a high-binding-capacity DNA aptamer group. An important point is that the aptamer group obtained included the thrombin-binding DNA aptamer M08, which had previously been shown in vitro to have maximum anticoagulation activity [Yoshimoto et al., Molecular Therapy Nucleic Acids, 16, 348-359 (2019)].

Evolutionary molecular engineering techniques in drug discovery

Apart from the SELEX method, there exist molecular-engineering-type molecule-selection methods that use molecular libraries of various modalities, from low molecular-weight compounds to antibodies. These include phage-display methods, liposome-display methods, mRNA-display methods, screening methods using DNA-encoded chemical libraries, and VHH antibody screening methods. MACE Separation is not in competition with the other technologies used in organic chemistry and biochemistry, but rather has the potential to be used in combination with all the above evolutionary-molecular-engineering-type selection methods to improve their quality.

MACE Separation technology explanatory documents

Currently in preparation