JULY 2021LIFE SCIENCES REVIEW 19However, on the flipside, DRPs have a complex structure with multiple SS bonds in the molecule, which acts as a hurdle in creating DRP libraries for screening and peptide engineering such as amino acid modification. In addition, synthesizing sufficient quantities of DRPs to evaluate the function of the hit DRPs has become a bottleneck, and hence, DRP drug discovery and development has not progressed as expected. Veneno Technologies' Veneno Suite addresses all of these challenges effectively.A One-Stop Solution for DRP Drug DevelopmentVeneno Suite's DRP Space, a gene-based library, uses natural DRP as templates and artificially adds random mutations to their DNA sequences using a proprietary algorithm to construct a massive library of the order of billion (ten to the power of nine). Its proprietary algorithms include an accelerated evolutionary approach similar to that used by venomous animals to evolve peptide toxins and in silico methods such as molecular surface charge and hydrophobicity based on 3D structural information, enabling the design and construction of diverse libraries. At the core of the Veneno Suite is the company's novel DRP high-throughput screening technology, PERISS--Intra Periplasm Secretion and Selection. It uses the periplasmic space between the inner and outer membranes of E. coli and employs periplasmic display technology based on molecular evolutionary engineering to enable rapid screening from a huge DRP library with one billion amino acid sequences produced by DRP Space. "Compared to conventional screening methods, PERISS dramatically increases the probability of obtaining highly active DRPs. In addition, it takes only about 12 months from the start of screening to the acquisition of hit DRP peptide sequences, which enables much more efficient and rapid screening than existing rapid electrophysiological methods," mentions Dr. Kimura. Besides, the PERISS method can also be used to search for fragment antibodies such as nanobody (VHH antibody), Fab antibodies, as well as IgG antibodies.In order to produce DRPs in large quantities at a low cost, Veneno Technologies is using E. coli that can correctly fold DRPs using periplasmic space. The team is developing a proprietary technology (IP patented), Super Secrete, to produce DRPs into the culture medium outside E. coli in collaboration with a Japanese chemical company. Super Secrete will significantly reduce the contamination of impurities and simplify the purification process. "At present, small-scale production at the laboratory level (cultivation and purification using a small jar-fermenter) has been established. In the future, we expect the Super Secrete technology to be applied to continuous cultivation methods and GMP production, making it an engine for realistically promoting DRP drug discovery," affirms Dr. Kimura.Paving the Way for a Better FutureEven though Veneno Technologies is only a year old, the firm has already succeeded in finding numerous new DRPs with inhibitory and facilitative effects on several ion channels using its innovative technology. For example, the firm recently demonstrated--electrophysiologically--how a newly discovered DRP molecule against a potassium channel with no known ligand acts on the target channel and completely inhibits its activation.In addition to the pharmaceutical business, the company also focuses on the R&D of green agricultural chemicals with low environmental impact. "In concrete, we have started joint research with a chemical company to create new bioactive peptides as new biostimulants and peptide-based drug-resistant insecticides. We are in charge of screening and conducting research to support sustainable agriculture in response to the recent climate change and population growth problems," states Dr. Kimura.Veneno Technologies' plan for the future is to invest in constant R&D and continuously improve existing technologies and develop new ones. Alongside, the company is looking to introduce robotics and AI in the library design and screening processes in order to maintain and strengthen its competitive advantage in the marketplace. "We are also actively seeking alliances with other organizations for related technologies and value the strategic investment and concentration of capital," wraps up Dr. Kimura. Compared to conventional screening methods, PERISS dramatically increases the probability of obtaining highly active DRPs
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