A5075930118- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- CRISPR and Genetic Engineering
- Viral gastroenteritis research and epidemiology
- CAR-T cell therapy research
- Liver physiology and pathology
- RNA Interference and Gene Delivery
- Animal Virus Infections Studies
- Organ Transplantation Techniques and Outcomes
- Pediatric Hepatobiliary Diseases and Treatments
- Hemophilia Treatment and Research
- SARS-CoV-2 and COVID-19 Research
- Trace Elements in Health
- Prion Diseases and Protein Misfolding
- Nuclear Receptors and Signaling
- Genetic and Kidney Cyst Diseases
- Phagocytosis and Immune Regulation
- Pancreatic function and diabetes
- Neurological diseases and metabolism
Istituti di Ricovero e Cura a Carattere Scientifico
2017-2025
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2017-2025
The San Raffaele Telethon Institute for Gene Therapy
2015-2025
Vita-Salute San Raffaele University
2016-2023
ORCID
2021
University Foundation
2013
Lentiviral vectors with high surface content of CD47 improved gene transfer efficiency to hepatocytes in nonhuman primates.
Liver gene therapy with adeno-associated viral (AAV) vectors delivering clotting factor transgenes into hepatocytes has shown multiyear therapeutic benefit in adults hemophilia. However, the mostly episomal nature of AAV challenges their application to young pediatric patients. We developed lentiviral vectors, which integrate host cell genome, that achieve efficient liver transfer mice, dogs and non-human primates, by intravenous delivery. Here we first compare engineered coagulation VIII...
Research Article23 August 2017Open Access Source DataTransparent process Genome editing for scalable production of alloantigen-free lentiviral vectors in vivo gene therapy Michela Milani San Raffaele Telethon Institute Gene Therapy, IRCCS Scientific Institute, Milan, Italy Vita Salute University, Search more papers by this author Andrea Annoni Sara Bartolaccini Mauro Biffi Fabio Russo Tiziano Di Tomaso Raimondi Johannes Lengler Baxalta (former Baxter) Innovation GmbH, Vienna, Austria Michael...
Pre-clinical humanized mouse models are a powerful tool to evaluate immunotherapies. NSG-SGM3 mice reconstituted with human stem cells (huSGM3) develop pronounced myeloid due transgenic expression of cell factor, granulocyte-macrophage colony-stimulating and interleukin-3 (IL-3) compared the widely used NSG (huNSG) model. We assessed in vivo generation CD19-CAR T huSGM3 upon single intravenous injection cell-specific lentiviral vectors (LVs) CD4-LV CD8-LV. While CAR was clearly detectable...
Abstract Lentiviral vectors (LV) are efficient vehicles for in vivo gene delivery to the liver. LV integration into chromatin of target cells ensures their transmission upon proliferation, thus allowing potentially life-long therapy following a single administration, even young individuals. The glycoprotein vesicular stomatitis virus (VSV.G) is widely used pseudotype LV, as it confers broad tropism and high stability. baculovirus-derived GP64 envelope protein has been proposed an alternative...
Abstract The liver is a central organ for metabolism and hepatocytes are the main cell type responsible most of its functions. Several previous studies investigated types involved in tissue homeostasis regeneration 1–4 , however mechanisms underlying post-natal growth establishment mature hepatocyte phenotypes remain to be fully understood. Here we investigate dynamics mice during adulthood, by spatial transcriptomics 5 clonal analysis, lineage tracing. We observe progressive metabolic...
Lentiviral vectors (LVs) are attractive vehicles for liver-directed gene therapy by virtue of their ability to stably integrate in the genome target cells and lack pre-existing immunity against vector components most humans. Over past years, we have developed a LV platform that can achieve stable transgene expression liver, induce transgene-specific immune tolerance establish correction hemophilia mouse models upon systemic administration. This is designed stringently hepatocytes through...
Lentiviral vectors (LVs) represent efficient and versatile vehicles for gene therapy. Current manufacturing of clinical-grade LVs mostly relies on transient transfection plasmids expressing the multiple vector components. This method is labor cost intensive becomes challenging when facing need scale-up standardization. The development stable LV producer cell lines will greatly facilitate overcoming these hurdles. We have generated an inducible packaging line, carrying genes encoding...
Lentiviral vectors (LVs) represent efficient and versatile vehicles for gene therapy. The manufacturing of clinical-grade LVs relies on transient transfection vector components. This method is labor cost intensive becomes challenging when facing the need scale-up standardization. development stable LV producer cell lines will greatly facilitate overcoming these hurdles. We have generated an inducible packaging line, carrying genes encoding third-generation components stably integrated in...
Lentiviral vectors (LVs) are attractive vehicles for liver-directed gene therapy by virtue of their ability to stably integrate in the genome target cells and low prevalence pre-existing immunity against HIV humans. Over past years, we have developed a LV platform that can achieve stable transgene expression liver, induce transgene-specific immune tolerance establish correction hemophilia mouse models upon systemic administration. This is designed stringently hepatocytes through...
Liver regeneration is supported by hepatocytes and, in certain conditions, biliary epithelial cells (BEC). BEC are bipotent stem cells, able to form organoids culture and engraft damaged livers. However, heterogeneity the homeostatic liver remains be fully elucidated. Here, we exploited vivo systemic lentiviral vector (LV) administration achieve efficient life-long gene transfer mice. We found that LV-marked retain organoid-formation potential respond damage, however, were less clonogenic...
Abstract Liver gene therapy with adeno-associated viral (AAV) vectors delivering a clotting factor transgene into hepatocytes has shown multi-year therapeutic benefit in adults hemophilia. However, anti-AAV pre-existing immunity and the mostly episomal nature of AAV vectors, currently challenges application AAV-vector mediated liver to people neutralizing antibodies young pediatric patients. We have developed lentiviral (LV), which integrate host cell genome, achieve stable efficient...