A5036091838- CRISPR and Genetic Engineering
- CAR-T cell therapy research
- Virus-based gene therapy research
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- Viral Infectious Diseases and Gene Expression in Insects
- Cytomegalovirus and herpesvirus research
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Pluripotent Stem Cells Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Immunodeficiency and Autoimmune Disorders
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Blood disorders and treatments
- Acute Myeloid Leukemia Research
- HIV Research and Treatment
- Mesenchymal stem cell research
- Viral gastroenteritis research and epidemiology
- Advanced biosensing and bioanalysis techniques
- Fungal Infections and Studies
- Cancer Genomics and Diagnostics
- Bacterial Infections and Vaccines
- Extracellular vesicles in disease
The San Raffaele Telethon Institute for Gene Therapy
2014-2024
Boston Children's Hospital
2021-2024
Boston Children's Museum
2021-2024
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2017-2024
Harvard University
2021-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2016-2024
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2021-2024
Dana-Farber Cancer Institute
2021-2024
Boston University
2022
Vita-Salute San Raffaele University
2008-2021
Precise gene editing in hematopoietic stem and progenitor cells (HSPCs) holds promise for treating genetic diseases. However, responses triggered by programmable nucleases HSPCs are poorly characterized may negatively impact HSPC engraftment long-term repopulation capacity. Here, we induced either one or several DNA double-stranded breaks (DSBs) with optimized zinc-finger CRISPR/Cas9 monitored damage response (DDR) foci induction, cell-cycle progression, transcriptional subpopulations, up to...
Preclinical studies establish the conditions for safe and effective correction of SCID-X1 by targeted gene editing hematopoietic stem cells.
Abstract Despite the considerable efficacy observed when targeting a dispensable lineage antigen, such as CD19 in B cell acute lymphoblastic leukaemia 1,2 , broader applicability of adoptive immunotherapies is hampered by absence tumour-restricted antigens 3–5 . Acute myeloid target genes expressed haematopoietic stem/progenitor cells (HSPCs) or differentiated cells, resulting intolerable on-target/off-tumour toxicity. Here we show that epitope engineering donor HSPCs used for bone marrow...
Abstract Human natural killer T cells (NKTs) are innate-like lymphocytes increasingly used for cancer immunotherapy. Here we show that human NKTs expressing the pro-inflammatory cytokine interleukin-12 (IL-12) undergo extensive and sustained molecular functional reprogramming. Specifically, IL-12 instructs maintains a Th1-polarization program in vivo without causing their exhaustion. Furthermore, using CD62L as marker of memory NKTs, observe long-term CD62L-expressing vivo. Notably,...
Abstract Lentiviral vectors are attractive tools for liver-directed gene therapy because of their capacity stable expression and the lack preexisting immunity in most human subjects. However, use integrating may raise some concerns about potential risk insertional mutagenesis. Here we investigated liver transfer by integrase-defective lentiviral (IDLVs) containing an inactivating mutation integrase (D64V). Hepatocyte-targeted using IDLVs resulted sustained robust induction immune tolerance...
Innate immune factors may restrict hematopoietic stem cell (HSC) genetic engineering and contribute to broad individual variability in gene therapy outcomes. Here, we show that HSCs harbor an early, constitutively active innate block lentiviral transduction can be efficiently overcome by cyclosporine H (CsH). CsH potently enhances transfer editing human long-term repopulating inhibiting interferon-induced transmembrane protein 3 (IFITM3), which restricts VSV glycoprotein-mediated vector...
Recombination activating genes ( RAGs ) are tightly regulated during lymphoid differentiation, and their mutations cause a spectrum of severe immunological disorders. Hematopoietic stem progenitor cell (HSPC) transplantation is the treatment choice but limited by donor availability toxicity. To overcome these issues, we developed gene editing strategies targeting corrective sequence into human RAG1 homology-directed repair (HDR) validated them tailored two-dimensional, three-dimensional, in...
Abstract Gene targeting is progressively becoming a realistic therapeutic alternative in clinics. It unknown, however, whether this technology will be suitable for the treatment of DNA repair deficiency syndromes such as F anconi anemia ( FA ), with defects homology‐directed repair. In study, we used zinc finger nucleases and integrase‐defective lentiviral vectors to demonstrate first time that FANCA can efficiently specifically targeted into AAVS1 safe harbor locus fibroblasts from ‐ A...
Article21 January 2021Open Access Source DataTransparent process Modeling, optimization, and comparable efficacy of T cell hematopoietic stem gene editing for treating hyper-IgM syndrome Valentina Vavassori San Raffaele Telethon Institute Gene Therapy, IRCCS Scientific Institute, Milan, Italy Vita-Salute University, ItalyThese authors contributed equally to this work Search more papers by author Elisabetta Mercuri Milano-Bicocca Monza, Genni E Marcovecchio Maria C Castiello Genetic...
Research Article12 September 2017Open Access Source DataTransparent process Therapeutic gene editing in CD34+ hematopoietic progenitors from Fanconi anemia patients Begoña Diez Division of Hematopoietic Innovative Therapies, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid, Spain Advanced Therapies Unit, Instituto Investigación Sanitaria Fundación Jiménez Díaz, Biomédica en Red Enfermedades Raras, Search for more papers by this author Pietro Genovese San...
Heterozygous mutations in CTLA-4 result an inborn error of immunity with autoimmune and frequently severe clinical phenotype. Autologous T cell gene therapy may offer a cure without the immunological complications allogeneic hematopoietic stem transplantation. Here, we designed homology-directed repair (HDR) editing strategy that inserts cDNA into first intron genomic locus primary human cells. This resulted regulated expression CD4 + cells, functional studies demonstrated CD80 CD86...
In adoptive T cell therapy, the long term therapeutic benefits in patients treated with engineered tumor specific cells are limited by lack of persistence infused cellular products and immunosuppressive mechanisms active microenvironment. Exhausted infiltrating characterized loss effector functions triggered multiple inhibitory receptors (IRs). patients, IR blockade reverts exhaustion but has low selectivity, potentially unleashing autoreactive clones resulting clinical autoimmune side...
Cytokine-induced killer (CIK) cells consist of a heterogeneous population polyclonal T lymphocytes displaying NK phenotype and HLA-unrestricted cytotoxic activity against broad range tumors. We sought to determine whether transduction CIK with cell receptor (TCR) genes specific for tumor-associated antigens could generate effector endowed double mechanism tumor recognition. HLA-A2-restricted TCR-transduced (TD) directed the melanoma Mart1 NY-ESO1 were generated by lentiviral successfully...