0000000000256485
AUTHOR
Robert C. Münch
showing 3 related works from this author
A Library-Based Screening Strategy for the Identification of DARPins as Ligands for Receptor-Targeted AAV and Lentiviral Vectors
2021
Delivering genes selectively to the therapeutically relevant cell type is among the prime goals of vector development. Here, we present a high-throughput selection and screening process that identifies designed ankyrin repeat proteins (DARPins) optimally suited for receptor-targeted gene delivery using adeno-associated viral (AAV) and lentiviral (LV) vectors. In particular, the process includes expression, purification, and in situ biotinylation of the extracellular domains of target receptors as Fc fusion proteins in mammalian cells and the selection of high-affinity binders by ribosome display from DARPin libraries each covering more than 1012 variants. This way, DARPins specific for the …
Exclusive transduction of human CD4+ T Cells upon systemic delivery of CD4-targeted lentiviral vectors
2015
Abstract Playing a central role in both innate and adaptive immunity, CD4+ T cells are a key target for genetic modifications in basic research and immunotherapy. In this article, we describe novel lentiviral vectors (CD4-LV) that have been rendered selective for human or simian CD4+ cells by surface engineering. When applied to PBMCs, CD4-LV transduced CD4+ but not CD4− cells. Notably, also unstimulated T cells were stably genetically modified. Upon systemic or intrasplenic administration into mice reconstituted with human PBMCs or hematopoietic stem cells, reporter gene expression was predominantly detected in lymphoid organs. Evaluation of GFP expression in organ-derived cells and blood …
566. Selective and Stable Transduction of Human CD4+ T Cells In Vivo Upon Systemic Administration of CD4-Targeted Lentiviral Vectors
2015
Playing a central role in both innate and adaptive immunity, CD4+ T cells are the key target for genetic modifications in basic research and immunotherapy. Specific and stable delivery of therapeutic genes into these cells is therefore highly desirable. Here, we describe novel lentiviral vectors (CD4-LV) that have been rendered selective for human or simian CD4+ cells by surface engineering. This novel CD4-LV was highly specific and effective in genetic modification of human CD4+ T cells both in vitro and in vivo. When applied to peripheral blood mononuclear cells (PBMC), CD4-LV transduced CD4+ but not CD4− cells. Notably, also unstimulated T cells were stably genetically modified. Upon sys…