To this end, we applied one of the most clinically relevant animal models for glioblastoma known. This model was established several years ago [20] and its growth pattern as well as geno-and phenotypic similarity to glioblastoma in patients has been extensively characterized [3] . A striking difference of our model compared to other cell-line based models is the highly invasive behaviour of the lesions, similar to glioblastoma in patients. Our model is based on spheroids derived from patient biopsies that are passaged serially in the brains of nude rats. First generation tumors are highly invasive and grow without signs of angiogenesis. Late generation tumors show an angiogenic phenotype, but are still invasive. Our in vitro experiments revealed that both lentiviral vectors transduced spheroids derived from both low and high generation tumors very efficiently. In contrast, retroviral vectors transduced only high generation spheroids and displayed a much lower efficiency of gene transfer than both lentiviral vectors. This difference can only be attributed to the vector backbone, as the glycoprotein which is responsible for virus entry into the cell was the same for the retroviral and one of the lentivral vectors applied (LCMV-GP). The most important feature that distinguishes lentiviral from retroviral vectors is their ability to infect non-dividing cells. It is known that glioma spheroids, especially primary biopsy spheroids, contain a significant fraction of non-dividing cells, which cannot be transduced by retroviral vectors. It has previously been shown that the cultured biopsy spheroids show a similar cell proliferation as seen in glioblastoma patients [20] .