Precise Drug Target Identification is a first step for improving efficacy, tracing and avoiding side-effects as well as understanding the mode-of-actions of drug candidates.
However, until now, effective systematic approaches for the precise drug target identification at genome levels have not been commercially available.
Using S. pombe genome-wide heterozygous deletion mutant library, Bioneer has developed a high-throughput genome-wide drug target screening service system (GPScreen™, Figure 1)
and made it commercially available for your drug discovery needs.
GPScreen™ screening service covers a broad spectrum of drug candidates in whole disease areas from cancers & metabolic diseases to neglected & rare diseases and, therefore,
will provide the total solutions for an efficient drug discovery through providing clear-cut answers to problems such as drug-target(s) and toxicity as well as mode-of-actions of drug candidates.
Figure 1. Schematic Diagram of Genome-wide Drug target Discovery with GPScreen™
Background of Development of a Genome-wide Drug Target Discovery Technology; GPScreen™
In cells, there is a myriad of proteins which might play a role as a drug target. It is estimated that there are about 20,000-30,000 genes in human cells, which correspond to 100,000 proteins when including the post-translationally modified proteins. Therefore, seeking a real target from a myriad of proteins is a very difficult job. But, there has been considered that an ideal solution for this problem would be to considered to measure drug responsiveness of each gene. However, the establishment of genome-wide deletion mutant library has remained a technological barrier.
In this regard, Bioneer has developed S. pombe genome-wide deletion mutant library—covering 98.5% of S. pombe entire genome of 4914 genes—in collaboration with Korea Research Institute of Biotechnology and Bioscience (KRIBB) and Dr. Paul Nurse of Cancer Research Center in UK by investing $ 10 M for 10 years (Nat. Biotech, 28, 2010). And using this mutant library, Bioneer has developed and commercialized the genome-wide drug target identification system, GPScreen™, in 2011, and opened up the new era of genome-wide drug target identification services1 .
"Bioneer's GPScreen™ using S. pombe genome-wide heterozygous deletion mutant library has enabled genome-wide screening for drug target identification"
Principle of GPScreen™
Drug-induced Haploinsufficiency (DIH)" is a situation in which a strain with a heterozygous gene deletion (producing target proteins
to about half of normal levels), result in cells sensitive to a specific drug. DIH occurs when a drug or drug candidate acts on a
mutant strain in which the level of target gene protein is lowered from normal to half level, and is considered to be a
valuable tool for drug target identification. Previously, a number of reports have provided identifications of drug
targets using DIH in budding yeast S. cerevisiae (Baetz K et al., 2004; Lum et al., 2004). However,
fission yeast S. pombe is considered a better model of mammalian cells since its cell cycle regulation is closer to that of mammalian cells than that of S. cerevisiae.
"GPScreen™ utilizes DIH in the fission yeast S. pombe genome-wide heterozygous deletion mutant library to identify the drug target(s).
Features & Benefits of GPScreen™ Technology
- World's unique & innovative technology
- Drug target screening at each gene level in about 5000 genes
- Live cell-based screening
- Drug target screening within average two weeks
- Rapid, accurate, & cost-effective screening
- Identify any classes of targets in genome through genome-wide screening
- Applicable to all areas of drug discovery; toxicity profiling, drug rescue/repositioning, natural drug target discovery
Process of Genome-wide Drug On/Off-target Discovery with GPScreen™ Technology
Since the establishment of GPScreen™ service system, Bioneer has been providing the service to domestic and global top tier pharmaceutical companies for drug target
identification. The detailed process Genome-wide Drug On/Off-target Discovery with GPScreen™ Technology of this service is as below (Figure 2).
Figure 2. Process of Genome-wide Drug Target Discovery with GPScreen™