Publications by authors named "K A Mitrophanous"

A wealth of high-throughput biological data, of which omics constitute a significant fraction, has been made publicly available in repositories over the past decades. These data come in various formats and cover a range of species and research areas providing insights into the complexities of biological systems; the public repositories hosting these data serve as multifaceted resources. The potentially greater value of these data lies in their secondary utilization as the deployment of data science and artificial intelligence in biology advances.

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Chimeric antigen receptor (CAR) T cells represent a novel targeted approach to overcome deficits in the ability of the host immune system to detect and subsequently eradicate tumors. The identification of antigens expressed specifically on the surface of tumor cells is a critical first step for a targeted therapy that selectively targets cancer cells without affecting normal tissues. 5T4 is a tumor-associated antigen expressed on the cell surface of most solid tumors.

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Lentiviral vectors are highly efficient gene delivery vehicles used extensively in the rapidly growing field of cell and gene therapy. Demand for efficient, large-scale, lentiviral vector bioprocessing is growing as more therapies reach late-stage clinical trials and are commercialized. However, despite substantial progress, several process inefficiencies remain.

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Both cell surface and soluble extracellular glycosaminoglycans have been shown to interfere with the exogenous nucleic acid delivery efficiency of non-viral gene delivery, including lipoplex and polyplex-mediated transfection. Most gene therapy viral vectors used commercially and in clinical trials are currently manufactured using transient transfection-based bioprocesses. The growing demand for viral vector products, coupled with a global shortage in production capability, requires improved transfection technologies and processes to maximise process efficiency and productivity.

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Article Synopsis
  • The demand for Lentiviral Vector (LV) drug substances is rising, but manufacturing challenges persist, especially in primary capture using anion-exchange chromatography due to complex adsorption behaviors.
  • Understanding the structural components of LVs, particularly the envelope components, is crucial for effective process design, as high binding heterogeneity influences elution profiles.
  • Eliminating the VSV-G protein did not affect the two-peak elution profile, while targeting glycosaminoglycans (GAGs) significantly altered the distribution of LVs in these peaks, indicating different binding interactions within discrete LV populations.
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