A5070158694- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Mosquito-borne diseases and control
- Viral Infections and Vectors
- Protist diversity and phylogeny
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- Microtubule and mitosis dynamics
- Diet and metabolism studies
- Pancreatic function and diabetes
- Hematopoietic Stem Cell Transplantation
- Genomics and Rare Diseases
- Gut microbiota and health
- bioluminescence and chemiluminescence research
- Immune cells in cancer
- Advanced biosensing and bioanalysis techniques
- Virology and Viral Diseases
- Nuclear Receptors and Signaling
Istituti di Ricovero e Cura a Carattere Scientifico
2021-2024
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2021-2024
The San Raffaele Telethon Institute for Gene Therapy
2021-2024
Whitehead Institute for Biomedical Research
2016-2021
Université Paris-Saclay
2018-2019
Slow progress in the fight against neurodegenerative diseases (NDs) motivates an urgent need for highly controlled vitro systems to investigate organ-organ- and organ-immune-specific interactions relevant disease pathophysiology. Of particular interest is gut/microbiome-liver-brain axis parsing out how genetic environmental factors contribute NDs. We have developed a mesofluidic platform technology study gut-liver-cerebral context of Parkinson's (PD). It connects microphysiological (MPSs)...
Base and prime editors (BEs PEs) may provide more precise genetic engineering than nuclease-based approaches because they bypass the dependence on DNA double-strand breaks. However, little is known about their cellular responses genotoxicity. Here, we compared state-of-the-art BEs PEs Cas9 in human hematopoietic stem progenitor cells with respect to editing efficiency, cytotoxicity, transcriptomic changes on-target genome-wide induced detrimental transcriptional that reduced efficiency...
Significance We describe the ability of Zika virus to infect various cells fetal brain, modeled from induced pluripotent stem derived a patient and grown in identical conditions. is associated with microcephaly, while similar dengue not. described differences behavior these two viruses. often fails trigger efficient antiviral responses, surviving encounters brain immune cells, killing immature nerve cell precursors that have poor innate defenses. Precursors brain’s microglia, circulating...
Significance Zika virus (ZIKV) is a neurotropic and neurovirulent arbovirus that has severe detrimental impact on the developing human fetal brain. We used genome-wide CRISPR-Cas9 knockout screen to identify ZIKV host genes in neural progenitors. The identified factors involved heparan sulfation, endocytosis, endoplasmic reticulum processing, Golgi function, interferon activity. Our findings provide insights into host-dependent mechanisms for infection highly vulnerable progenitor cells...
Hematopoietic stem/progenitor cell gene therapy (HSPC-GT) is proving successful to treat several genetic diseases. HSPCs are mobilized, harvested, genetically corrected ex vivo, and infused, after the administration of toxic myeloablative conditioning deplete bone marrow (BM) for modified cells. We show that mobilizers create an opportunity seamless engraftment exogenous cells, which effectively outcompete those repopulate depleted BM. The competitive advantage results from rescue during...
Most genes mutated in microcephaly patients are expressed ubiquitously, and yet the brain is only major organ compromised most patients. Why phenotype remains specific poorly understood. In this study, we used vitro differentiation of human embryonic stem cells to monitor effect a point mutation kinetochore null protein 1 (KNL1; CASC5), identified patients, during development. We found that neural progenitors bearing patient showed reduced KNL1 levels, aneuploidy, an abrogated spindle...
Topic: 24. Gene therapy, cellular immunotherapy and vaccination - Biology & Translational Research Background: Emerging base prime editing (BE/PE) may provide safer more precise genetic engineering than nuclease-based approaches bypassing the dependence on DNA double strand breaks (DSBs). Aims: However, comprehensive characterization of efficiency, tolerability genotoxicity these platforms is lacking relevant to instruct safe clinical application. Methods: Here, we comparatively assessed...