Project description:The safety and efficacy of a recombinant adeno-associated virus derivative (rAAVr3.45) were examined to evaluate its potential as a gene carrier for preparing interleukin-10 (IL10)-secreting human neural stem cells (HFT13) that can treat ischemic injuries or neurodegenerative diseases.
Project description:Hepatocellular carcinomas (HCC) are liver tumors related to various etiologies including alcohol intake, hepatitis B (HBV) or C (HCV) virus infection. Additional risk factors remain to be identified, particularly in patients who develop HCC without cirrhosis. We identified clonal integration of adeno-associated virus type 2 (AAV2) in 11 out of 193 HCC. These AAV2 integrations occurred within known cancer driver genes, namely, CCNA2 (Cyclin A2, 4 cases), TERT (Telomerase Reverse-Transcriptase, 1 case), CCNE1 (Cyclin E1, 3 cases), TNFSF10 (Tumor Necrosis Factor member 10, 2 cases) or KMT2B (Lysine (K)-Specific Methyltransferase 2B, 1 case) leading to over-expression of the target genes. Tumors with viral integration mainly developed in non-cirrhotic liver (9 out of 11 cases) and without known risk factors (6 out of 11) suggesting a pathogenic role of AAV2 in these patients. In conclusion, AAV2 is a DNA virus associated with oncogenic insertional mutagenesis in human HCC.
Project description:After initial infection at mucosa, herpes simplex virus (HSV) establishes lifelong latency in neurons of the peripheral nervous system, which represents the source of recurrent disease. Current antiviral therapies reduce symptoms and viral shedding, but do not cure the infection. In contrast, gene editing offers the possibility to lethally mutate or even eliminate latent viral genomes. Delivery of gene editing enzymes by Adeno Associated Virus (AAV) vectors represents a promising approach to functionally curing HSV infection. In order to optimize in vivo gene therapy approaches it is necessary to understand which neuronal subtypes within peripheral ganglia are infected by HSV and which subtypes are efficiently targeted by various AAV serotypes. Here we use single cell RNA sequencing (scRNA-seq) to identify neurons expressing HSV genes as well as reporter genes for AAV1, AAV8, AAV-PhP.s, and AAV-Rh10 serotypes.
