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Drugs in Development
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Drugs in Development
OyaGen seeks to induce transient and beneficial changes in the protein expression of human tissues by involving the editing enzymes in targeting biomedically relevant pathways.
OyaGen’s platform technology encompasses a family of fourteen (14) editing enzymes and the proteins that modulate their activity. The function of many of these enzymes is unexplored as yet, however several of the enzymes have been extensively studied with encouraging results for this approach. The enzymes that have been studied are known to affect a range of important functions including antiviral, cancer, immunoglobulin gene rearrangements, inflammation, ion channel function, LDL reduction, neuro-cognitive functions and red blood cell expression in fetal liver.
Intellectual property developed by Drs. Harold C. Smith (University of Rochester, Rochester, NY) and Hui Zhang (Thomas Jefferson University, Philadelphia, PA) have been combined in OyaGen as the basis for the editing enzyme technology. Both of these creative scientific innovators are presently affiliated with OyaGen.
Vif Dimerization Antagonist
OyaGen holds an exclusive license from Thomas Jefferson University (TJU) covering a 'lead' peptide sequence that functions to inhibit the activity of the HIV-1 protein known as Vif (viral infectivity factor). OyaGen’s peptide is referred to as Vif Dimerization Antagonist (VDA) and is a Vif mimetic that antagonizes dimerization of Vif. As a result of the inability of Vif to form a dimer, the host defense editing enzyme known as hA3G catastrophically mutates the HIV-1 genome and significantly reduces its ability to replicate and infect.VDA consists of a peptide sequence capable of competing with Vif for Vif homodimer formation and a protein transduction domain enabling cell uptake. OyaGen’s current lead VDA has reduced HIV-1 life viral infectivity 2-3 orders of magnitude compared to controls in all human systems evaluated. The data suggests that the dimerization domain of Vif is one of the most important AIDS therapeutic targets of this century. It may out perform other AIDS therapeutics because the requirement of Vif dimerization for the control of cellular hA3G restricts the degrees of freedom otherwise afforded to the virus by its mutation frequency. The Vif dimerization domain is covered by one of the Company’s patents. OyaGen, Inc is a new start-up and is in the process of establishing an appropriate infrastructure to support execution of its business plan. In the interim the laboratories of Drs. Smith and Zhang at the URMC and TJU, respectively are optimizing VDA using live virus and pseudotyped virus to quantify viral infectivity by ELISA and flow cytometric analyses. Western blotting is used to assess Vif and hA3G expression levels. DNA and RNA sequence analyses and real time PCR have been employed to assess mRNAs and DNAs relevant to the process. This work is being undertaken as contract research and with NIH funding.
OyaGen, Inc plans to develop VDA to an optimized lead compound and enter non-human primate toxicity screens this year. Further VDA optimization will be to develop peptoids. VDA is an injectable in its current form.
The Company plans to initiate High Throughput Screening (HTP) for small molecules reactive with the VDA sequence. A suitable development partner is sought to identify and optimize small molecule Vif antagonist (SMVA).
