Miltenyi texmacs9/19/2023 ![]() ![]() To confer specific target cell entry, the viral attachment proteins of the MV and Nipah virus are mutated to abolish binding to their natural receptors. In contrast to VSV-G LVs, the function of attachment and fusion is separated on two glycoproteins, H or G and the F protein, respectively. One promising approach is using LVs pseudotyped with paramyxovirus envelope glycoproteins, e.g., Measles morbillivirus (MV), Nipah virus, or Tupaia paramyxovirus. To date, various strategies were developed to restrict gene transfer to a cell type of interest using cell-type-specific LVs. Therefore, limiting the gene transfer to the target cell population only may improve the safety and efficacy of a CAR-T cell therapy. Ruella and colleagues showed that off-target transduction represents a major risk factor in CAR-T cell production, as the transduction of a single leukemic B cell led to resistance to CAR-T cells. For instance, a shorter ex vivo expansion phase and the transduction of naïve T-cell subsets was shown to increase CAR-T cell efficacy. Improving this production process could result in a CAR-T cell product with enhanced efficacy. Consequently, the generation of CAR-T cells requires sophisticated ex vivo production protocols starting with T-cell isolation, activation, and gene transfer, followed by an expansion phase. Importantly, while many cell types readily express LDLR, T cells require activation to induce upregulation for sufficient transduction. As LDLR is expressed by many cell types, VSV-G confers broad tropism to LVs, making the isolation of the desired cell type necessary prior to transduction. VSV-G pseudotyped LVs require the expression of the low-density lipoprotein receptor (LDLR) for target cell binding and fusion. State-of-the-art LVs are pseudotyped with the glycoprotein G of vesicular stomatitis virus (VSV-G). This promising cancer immunotherapy showed exceptional clinical results, which led to the FDA approval of five therapies for the treatment of leukemia, lymphoma, and myeloma to date. These advantages make LVs attractive for generating chimeric antigen receptor (CAR)-T cell therapies. Lentiviral vectors (LVs) are a versatile tool for the genetic modification of mammalian cells, as they enable the transduction of dividing or non-dividing cells with sustained gene expression. Retrieved from Īuthor(s): Nicole Cordes Nora Winter Carolin Kolbe Bettina Kotter Joerg Mittelstaet Mario Assenmacher Toni Cathomen Andrew Kaiser Thomas Schaser (corresponding author) APA style: Adapter-Mediated Transduction with Lentiviral Vectors: A Novel Tool for Cell-Type-Specific Gene Transfer. ![]() Adapter-Mediated Transduction with Lentiviral Vectors: A Novel Tool for Cell-Type-Specific Gene Transfer." Retrieved from MLA style: "Adapter-Mediated Transduction with Lentiviral Vectors: A Novel Tool for Cell-Type-Specific Gene Transfer." The Free Library. ![]()
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