Human Genome Project: Discovery of New Drugs

Ming-Shi Chang

《Journal of Genetics and Molecular Biology》 11卷1期 (2000/03) Pp. 45-46

https://doi.org/10.30047/JGMB.200003.0009

並列摘要

Genomics will surpass the recombinant DNA era for generating therapeutic product opportunities. It will also be a key core technological competency for all therapeutic area. To determine biological functions of novel genes and to develop the therapeutic drugs for human diseases, we have applied various techniques and discovered the potential drugs. In my talk, I will give two examples how we determined the biological functions of the novels genes.
Osteoprotegerin (OPG) is a novel molecule isolated from the human genome (EST) project. This molecule shares homology with tumor necrosis factor receptor. In vivo, over expression of OPG in the transgenic mice results in a profond osteopetrosis, coincident with a decrease in later stage of osteoclast differentiation. These same effects are observed upon administration of recombinant OPG into normal mice. In vitro, osteoclast differentiation from precursor cells is blocked in a dose-dependent manner by recombinant OPG. Furthermore, OPG blocks ovariectomy-associated bone loss in rat. These data show that OPG can act as a soluble factor in the regulation of bone loss and imply a utility for OPG in the treatment of osteoporosis. Currently, OPG has been in the phase III clinical trial for osteoporosis.
NNT-1/BSF-3 is another novel molecule isolated from cDNA library of the activated T lymphoma cells. It is novel member of the IL-6 cytokine family. Over expression of the gene in transgenic mice induced proliferation of lymphoid tissue particularly in the speen and lymph node. It also increased blood B cells number in transgenic mice. In vitro study showed that NNT-1/BSF-3 also supported differentiation of chicken embryonic motor and sympathetic neurons. In vivo, it potentiated the induction by IL-1 of corticosterone and IL-6. Administration of the recombinant protein to the mice also induced b cells hyperplasia with serum IgG and IgM increase showing the same effect as in the transgenic mice.
Currently, we are in the process of isolating several other novel growth factors and cytokine receptors. These molecules may have some relation with cancer biology, bone formation or wound healing. Determination of their biological functions and further development of potential drug are in progress.
In summary, these studies demonstrate that human genome project is a good source for the discovery of potential drugs. Functional genomics will not only give us a revolutionary influence in understanding the biology of the novel genes but also greatly facilitate the development of new drugs for therapeutics in the 21th century.