Publications by authors named "M Themis"
Article Synopsis
- Regulators and industry experts are looking for better ways to assess the cancer-causing potential of gene therapies, as current methods may not be sufficient.
- A meeting in London in March 2023 brought together specialists to reach a consensus on key themes such as vector genotoxicity, uncertainty sources, and appropriate toxicological endpoints for gene therapy evaluation.
- The recommendations from this meeting aim to guide the creation of new regulatory guidelines for the nonclinical toxicological assessment of gene therapy products.
HIV-1 based lentiviral viruses are considered powerful and versatile gene therapy vectors to deliver therapeutic genes to patients with hereditary or acquired diseases. These vectors can efficiently transduce a variety of cell types when dividing or non-dividing to provide permanent delivery and long-term gene expression. Demand for scalable manufacturing protocols able to generate enough high titre vector for widespread use of this technology is increasing and considerable efforts to improve vector production cost-effectively, is ongoing.
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- Lentiviral vectors (LV) are promising tools for gene therapy, but can lead to insertional mutagenesis, making it crucial to study their integration into host genomes.
- The research focuses on how transcription factors (TF) may influence the process of LV integration by mapping predicted binding sites near the insertion points chosen by HIV-1 LV in human induced pluripotent stem cells and their derivatives.
- Findings indicate that specific transcription factor binding sites (pTFBS) are enriched in the LV insertion sites and are essential for the HIV-1 life cycle, suggesting their importance in viral survival and propagation.
Article Synopsis
- * Traditional cell lysates require purification methods, like caesium chloride or chromatography, but have limitations such as poor infectiousness and restricted storage capability.
- * An innovative aqueous two-phase system (ATPS) using 20% PEG 600 and 20% (NH)SO has been shown to efficiently purify AdVs, yielding over 97% high-titre virus with no cytotoxic effects, and stable storage at -20 °C or 4 °C for future clinical
The development of renewable sources of liver tissue is required to improve cell-based modelling, and develop human tissue for transplantation. Human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) represent promising sources of human liver spheres. We have developed a serum free and defined method of cellular differentiation to generate three-dimensional human liver spheres formed from human pluripotent stem cells.
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