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Virus Filtration Development for Adeno-Associated Virus-Based Gene Therapy Products.
Biotechnol J
January 2025
Drug Substance Development, Spark Therapeutics, Inc., Philadelphia, USA.
Adeno-associated virus (AAV) vectors have become a leading platform for gene delivery. A major portion of gene therapy currently in clinical trials are AAV-based for a wide range of diseases. A commonly used method for AAV production is by mammalian or insect cell culture, with or without added viruses to introduce needed genetic elements for AAV production.
View Article and Find Full Text PDF[Methods to Increase the Efficiency of Knock-in of a Construct Encoding the HIV-1 Fusion Inhibitor, MT-C34 Peptide, into the CXCR4 Locus in the CEM/R5 T Cell Line].
Mol Biol (Mosk)
December 2024
Center of Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334 Russia.
The low knock-in efficiency, especially in primary human cells, limits the use of the genome editing technology for therapeutic purposes, rendering it important to develop approaches for increasing the knock-in levels. In this work, the efficiencies of several approaches were studied using a model of knock-in of a construct coding for the peptide HIV fusion inhibitor MT-C34 into the human CXCR4 locus in the CEM/R5 T cell line. First, donor DNA modification was evaluated as a means to improve the efficiency of plasmid transport into the nucleus.
View Article and Find Full Text PDFPolyomavirus large T antigens: Unraveling a complex interactome.
Tumour Virus Res
December 2024
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, 15260, USA. Electronic address:
Article Synopsis
- All polyomaviruses produce a large T antigen (LT) protein that is crucial for viral DNA replication, gene regulation, and influencing cellular functions.
- Over 100 polyomaviruses exist, with 14 known to infect humans, yet most research on LT focuses on simian virus 40 (SV40) and a few others.
- This review emphasizes the differences and similarities among LT proteins of human polyomaviruses and identifies gaps in our knowledge, particularly due to the limited studies on LT proteins from various polyomavirus species.
Clusterin Deficiency Promotes Cellular Senescence in Human Astrocytes.
Mol Neurobiol
December 2024
Department of Physiology, Faculty of Science, Charles University, Prague, 128 00, Czech Republic.
Article Synopsis
- - The study focuses on the glycoprotein clusterin (CLU), which is important for cell growth and repairing DNA, and its effects on human astrocytic cell lines, showing that suppressing CLU leads to decreased cell growth and increased DNA damage response.
- - Researchers found that reducing CLU levels caused oxidative stress and triggered cellular aging (senescence) in astrocytoma cells and normal astrocytes, impacting mitochondrial function and altering energy production markers.
- - The findings highlight the crucial role of CLU in maintaining the cell cycle in astrocytes, suggesting that targeting CLU could be a promising strategy for treating gliomas (a type of brain tumor).
Conditional Immortalization Using SV40 Large T Antigen and Its Effects on Induced Pluripotent Stem Cell Differentiation Toward Retinal Progenitor Cells.
Stem Cells Dev
January 2025
Roy J. Carver Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa, USA.
Article Synopsis
- * The study aimed to create conditionally immortalized RPCs from human induced pluripotent stem cells (iPSCs) using a Tet-On system, which increased cell proliferation but negatively impacted RPC identity.
- * Findings show that the process of immortalization led to irreversible de-differentiation of RPCs despite attempts to revert changes, highlighting the need for better strategies to balance cell growth and differentiation for effective RPC use in therapies.
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