A5014745527- Virus-based gene therapy research
- Hepatitis B Virus Studies
- Hepatitis C virus research
- Herpesvirus Infections and Treatments
- CAR-T cell therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Liver Disease Diagnosis and Treatment
- Viral gastroenteritis research and epidemiology
- Cytomegalovirus and herpesvirus research
- Viral Infections and Outbreaks Research
- RNA Research and Splicing
- Viral Infections and Immunology Research
- T-cell and Retrovirus Studies
- Hepatitis Viruses Studies and Epidemiology
- Animal Virus Infections Studies
- Alzheimer's disease research and treatments
- interferon and immune responses
- Computational Drug Discovery Methods
- RNA and protein synthesis mechanisms
- Animal Disease Management and Epidemiology
- Animal Genetics and Reproduction
- Lysosomal Storage Disorders Research
Inserm
2015-2025
Université Claude Bernard Lyon 1
2014-2024
Centre International de Recherche en Infectiologie
2013-2024
Centre National de la Recherche Scientifique
2014-2024
École Normale Supérieure de Lyon
2012-2024
Centre de Recherche en Cancérologie de Lyon
2017-2023
Centre Léon Bérard
2018-2022
Oxford University Hospitals NHS Trust
2016
Université de Lyon
2015
Gene Therapy Laboratory
1997-2005
Recombinant adeno-associated virus (rAAV) is produced by transfecting cells with two constructs: the rAAV vector plasmid and rep-cap plasmid. After subsequent adenoviral infection, needed for replication assembly, purified from total cell lysates through CsCl gradients. Because this a long complex procedure, precise titration of stocks, as well measure level contamination adenovirus rep-positive AAV, are essential to evaluate transduction efficiency these vectors in vitro vivo. Our core...
We previously documented persistent regulation of erythropoietin (Epo) secretion in mice after a single intramuscular (i.m.) injection recombinant adeno-associated virus (rAAV) vector harboring both the tetracycline-dependent transactivator (rtTA) and Epo cDNA (D. Bohl, A. Salvetti, P. Moullier, J. M. Heard, Blood 92:1512-1517, 1998). Using same cynomolgus macaque instead, present study evaluated ability tetracycline-regulatable (tetR) system to establish long-term transgene nonhuman...
Nipah virus (NiV) and Hendra (HeV) are closely related, recently emerged paramyxoviruses that capable of causing considerable morbidity mortality in several mammalian species, including humans. Henipavirus-specific vaccines still commercially unavailable, development novel antiviral strategies to prevent lethal infections due henipaviruses is highly desirable. Here we describe the adeno-associated (AAV) expressing NiV G protein. Characterization these mice demonstrated a single intramuscular...
Abstract AAV vectors poorly transduce Dendritic cells (DC), a feature invoked to explain AAV’s low immunogenicity. However, the reason for this non-permissiveness remained elusive. Here, we performed an in-depth analysis using human monocyte-derived immature DC (iDC) as model. iDC internalized of various serotypes, but even most efficient serotype failed above background. Since reached cell nucleus, hypothesized that intracellular processing occurs suboptimal. On basis, screened peptide...
Abstract Current therapies for chronic hepatitis B virus (HBV) infections are effective at decreasing the viral load in serum, but do not lead to eradication. Recent studies highlighted therapeutic or “adjuvant” potential of immune-modulators. Our aim was explore direct anti-HBV effect Toll-Like-Receptors (TLR) agonists hepatocytes. HBV-infected primary human hepatocytes (PHH) differentiated HepaRG cells (dHepaRG) were treated with various TLR agonists. Amongst all ligands tested, Pam3CSK4...
Previous studies on distribution and toxicity of viral vectors administered in monkeys indicated that the nonhuman primate model has a reasonable predictive value for clinical applications. In this study, eight macaques were injected intramuscularly with recombinant adeno-associated virus (rAAV) at doses similar to those hemophilia B patients, followed analyze dissemination shedding biological samples long-term persistence distant organs. Following rAAV delivery, we found vector genome...
Abstract Lytic infection with herpes simplex virus type 1 (HSV-1) induces profound modification of the cell nucleus including formation a viral replication compartment and chromatin marginalization into nuclear periphery. We used three-dimensional soft X-ray tomography, combined cryogenic fluorescence, confocal electron microscopy, to analyse transformation peripheral during HSV-1 infection. Our data showed an increased presence low-density gaps in marginalized at late Advanced analysis...
Nucleolin (NCL) is a major component of the cell nucleolus, which has ability to rapidly shuttle several other cells' compartments. NCL plays important roles in variety essential functions, among are ribosome biogenesis, gene expression, and growth. However, precise mechanisms underlying functions still unclear. Our study aimed provide new information on via identification its nuclear interacting partners. Using an interactomics approach, we identified 140 proteins co-purified with NCL, 100...
Despite the existence of a preventive vaccine, chronic infection with Hepatitis B virus (HBV) affects more than 250 million people and represents major global cause hepatocellular carcinoma (HCC) worldwide. Current clinical treatments, in most cases, do not eliminate viral genome that persists as DNA episome nucleus hepatocytes constitutes stable template for continuous expression genes. Several studies suggest that, among factors, HBV core protein (HBc), well-known its structural role...
RNA helicase DDX5 is downregulated during HBV replication and poor prognosis HBV-related hepatocellular carcinoma (HCC). The objective of this study to investigate the role in interferon (IFN) signalling. We provide evidence a novel mechanism involving that enables translation transcription factor STAT1 mediating IFN response.
Recombinant adeno-associated virus vectors (rAAV) have been successfully used for long-term gene expression in animal models and patients. However, while the therapeutic potential of rAAV appears promising, safety issues, including contaminants found vector stocks, must be further evaluated. We previously reported that a cis-acting replication element present within AAV-2 p5 promoter was responsible encapsidation rep–cap sequences observed during production. In study, we also noticed...
Background A possible procedure for the production of clinical grade recombinant adeno-associated virus type 2 (rAAV) would include use packaging cell lines, harboring rep-cap genes and vector, combined with a replication defective adenoviral plasmid to provide helper activities. Several studies have already shown that rAAV can be efficiently assembled by infecting stable line adenovirus. However, direct comparison an has never been reported. Methods To investigate this point, clone HeLa 293...
Different liver cell types are endowed with immunological properties, including cell-intrinsic innate immune functions that important to initially control pathogen infections. However, a full landscape of expression and functionality the signaling pathways in major human cells is still missing. In order comparatively characterize these pathways, we purified primary hepatocytes, hepatic stellate cells, sinusoidal endothelial (LSEC), Kupffer (KC) from resections. We assessed mRNA protein level...
Here we describe the development of a two-step chromatography process based on use ion-exchange resins for purification recombinant adeno-associated virus (rAAV) serotypes-2 and -5. In vitro in vivo results demonstrate that this method, which does not require any prepurification step cell lysate, can be applied to obtain highly pure rAAV2 rAAV5 stocks. As such, procedure easily transferred vector cores also scaled up, allowing direct comparison these two, potentially other, AAV serotypes...
The human parvovirus Adeno-Associated Virus (AAV) type 2 can only replicate in cells co-infected with a helper virus, such as Adenovirus or Herpes Simplex 1 (HSV-1); whereas, the absence of it establishes latent infection. Previous studies demonstrated that ternary HSV-1 helicase/primase (HP) complex (UL5/8/52) and single-stranded DNA-Binding Protein (ICP8) were sufficient to induce AAV-2 replication transfected cells. We independently showed that, context infection, ICP0 protein was able...