Penta-IO Immunogenicity Optimizer Platform for Gene Therapy
Disease Background: Gene Therapy involves the transfer of genetic material into either somatic or germ-line cells; with the current science evolving to safer use of gene therapy the breath of opportunities for drug discovery has become wider. With over 20 approved Gene Therapy drugs by now, there is a stronger focus from the scientific community to bring more drugs to market using gene therapy. However, there are several hurdles such as leaky expression of viral proteins, loss of therapeutic gene expression, insertional mutagenesis and interference with the chromosome structure. To combat these hurdles, several technologies have been put in place to reinforce efficient viral delivery of therapeutic gene, be it Adenovirus, Adeno Associate Virus, Lentivirus or Herpes Simplex Virus. Using these technologies there has been a significant success with approved gene therapies reaching the market faster. However, they are also accompanied with adverse effects such as pyrexia, autoimmunity, muscle inflammation, myalgia, inflammatory maculopathy, cytokine release syndrome and meningitis in some cases.
Details on the Model: Pentagrit Immunogenicity Optimizer platform focus on refining gene therapies to be non-immunogenic in a human environment. Towards this the model zebrafish is grafted with equivalent target human tissue cells to enable viral entry and multiplication. Within a 96-hour period, reads outs are obtained from the fish that indicates level of immunogenicity of the gene therapy. Inflammatory indicators include granulocyte count, macrophage and leukocyte counts in the systemic circulation, associated serum inflammatory biomarkers, pathology such as pyrexia, and inflammatory infiltration with sepsis, vascular injury and infections. Hence a wide range of quantified evaluations is possible to identify the right gene therapy package that would be safe in a human disease condition.