Real-time definition of non-randomness in the distribution of genomic events. Efficient Tet-dependent expression of human factor IX in vivo by a new self-regulating lentiviral vector. Expression and prognostic role of tumor suppressor gene PTEN/MMAC1/TEP1 in hepatocellular carcinoma. Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. Hepatocellular carcinoma pathogenesis: from genes to environment. INK4a-ARF alterations and p53 mutations in hepatocellular carcinomas. In vivo administration of lentiviral vectors triggers a type I interferon response that restricts hepatocyte gene transfer and promotes vector clearance. Role of the INK4a locus in tumor suppression and cell mortality. Efficient gene delivery and targeted expression to hepatocytes in vivo by improved lentiviral vectors. Transplantation of genetically corrected human iPSC-derived progenitors in mice with limb-girdle muscular dystrophy. Correction of laminin-5 deficiency in human epidermal stem cells by transcriptionally targeted lentiviral vectors. Lentiviral transduction of the murine lung provides efficient pseudotype and developmental stage-dependent cell-specific transgene expression. 'Advanced' generation lentiviruses as efficient vectors for cardiomyocyte gene transduction in vitro and in vivo. Multiply attenuated, self-inactivating lentiviral vectors efficiently transduce human coronary artery cells in vitro and rat arteries in vivo. Design and optimization of lentiviral vectors for transfer of GALC expression in Twitcher brain. Cerebellar neurons and glial cells are transducible by lentiviral vectors without decrease of cerebellar functions. Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Naldini, L., Blomer, U., Gage, F.H., Trono, D. The genotoxic potential of retroviral vectors is strongly modulated by vector design and integration site selection in a mouse model of HSC gene therapy. High-throughput insertional mutagenesis screens in mice to identify oncogenic networks. The newly identified genes are likely to play a role in human cancer because they are upregulated, amplified and/or deleted in human HCCs and can predict clinical outcomes of patients. We validated the oncogenic potential of all the identified genes in vivo, with different levels of penetrance. By virtue of the LVV's replication-deficient nature and broad genome-wide integration pattern, LVV-based insertional mutagenesis allowed identification of four previously unknown liver cancer–associated genes from a limited number of integrations. We developed an insertional mutagenesis platform based on lentiviral vectors (LVVs) by which we could efficiently induce hepatocellular carcinoma (HCC) in three different mouse models. However, these systems are characterized by recurring integrations that accumulate in tumor cells and that hamper the identification of early cancer-driving events among bystander and progression-related events. Transposons and γ-retroviruses have been efficiently used as insertional mutagens in different tissues to identify molecular culprits of cancer.
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