A5012392416- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- HIV Research and Treatment
- CAR-T cell therapy research
- Cancer Research and Treatments
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Genomics and Diagnostics
- Immune responses and vaccinations
- Biomarkers in Disease Mechanisms
- Viral gastroenteritis research and epidemiology
- RNA Interference and Gene Delivery
- T-cell and B-cell Immunology
- Influenza Virus Research Studies
- Histiocytic Disorders and Treatments
- RNA modifications and cancer
- Testicular diseases and treatments
- Histone Deacetylase Inhibitors Research
- Plant nutrient uptake and metabolism
- Mast cells and histamine
- Heat shock proteins research
- COVID-19 Clinical Research Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune cells in cancer
The San Raffaele Telethon Institute for Gene Therapy
2013-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2017-2024
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2021-2024
IRCCS Ospedale San Raffaele
2022
Istituto Giannina Gaslini
2021
Vita-Salute San Raffaele University
2021
Istituto Nazionale Genetica Molecolare
2012
Gene therapy with lentiviral vectors targeting transgene expression to hepatocytes provides stable reconstitution of clotting activity in dogs hemophilia B and does not show genotoxicity tumor-prone mice.
Given the relevant role of extracellular microenvironment in regulating tissue homeostasis, is testicular bacterial microbiome (BM) associated with germ cell aplasia idiopathic non-obstructive azoospermia (iNOA)?A steady increase dysbiosis was observed among testis normal spermatogenesis vs. iNOA positive sperm retrieval and complete aplasia.Tissue-associated BM has been reported to be a biologically important component for numerous body habitats, but not yet human testis.Cross-sectional...
HIV-1 insertions targeting BACH2 or MLK2 are enriched and persist for decades in hematopoietic cells from patients under combination antiretroviral therapy. However, it is unclear how these provide such selective advantage to infected cell clones. Here, we show that 30/87 (34%) therapy, BACH2, STAT5B activated by triggering the formation of mRNAs contain viral sequences fused splicing their first protein-coding exon. These chimeric mRNAs, predicted express full-length proteins, T regulatory...
Abstract Hematopoietic stem cell gene therapy (GT) using a γ-retroviral vector (γ-RV) is an effective treatment for Severe Combined Immunodeficiency due to Adenosine Deaminase deficiency. Here, we describe case of GT-related T-cell acute lymphoblastic leukemia (T-ALL) that developed 4.7 years after treatment. The patient underwent chemotherapy and haploidentical transplantation currently in remission. Blast cells contain single insertion activating the LIM-only protein 2 ( LMO2)...
ABSTRACT Activating mutations in the BRAF-MAPK pathway have been reported histiocytoses, hematological inflammatory neoplasms characterized by multi-organ dissemination of pro-inflammatory myeloid cells. Here, we generate a humanized mouse model transplantation human hematopoietic stem and progenitor cells (HSPCs) expressing activated form BRAF ( V600E ). All mice transplanted with -expressing HSPCs succumb to bone marrow failure, displaying myeloid-restricted hematopoiesis aberrant...
The high transduction efficiency of lentiviral vectors in a wide variety cells makes them an ideal tool for forward genetics screenings addressing issues cancer research. Although molecular targeted therapies have provided significant advances tumor treatment, relapses often occur by the expansion cell clones carrying mutations that confer resistance. Identification culprits anticancer drug resistance is fundamental achievement long-term response. Here, we developed new vector-based...
Abstract Viral vectors are used to insert genetic material into semirandom genomic positions of hematopoietic stem cells which, after reinfusion patients, regenerate the entire system. Hematopoietic originating from genetically modified will harbor insertions in specific called integration sites, which represent unique marks clonal identity. Therefore, analysis vector sites present DNA circulating allows determine number clones blood ecosystem. Shannon diversity index is adopted evaluate...
O6-Methylguanine-DNA-Methyltransferase (MGMT) is a DNA repair protein considered to be chemosensitivity predictor. We evaluated the immunohistochemical MGMT expression in 28 consecutive oligodendroglial tumors (21 oligodendrogliomas, 5 mixed oligoastrocytomas, and 2 glioblastomas with prominent features; 13 treated CCNU) compared it that of glioblastomas. Twenty-six (93%) were MGMT-negative, (7%) MGMT-positive. Twelve (92%) patients CCNU had MGMT-negative lesions their median survival was 73...
Summary The humoral arm of innate immunity includes diverse molecules with antibody-like functions, some which serve as disease severity biomarkers in COVID-19. present study was designed to conduct a systematic investigation the interaction fluid phase pattern recognition (PRM) SARS-CoV-2. Out 10 PRM tested, long pentraxin PTX3 and Mannose Binding Lectin (MBL) bound viral Nucleoprotein Spike, respectively. MBL trimeric including that variants concern, glycan- dependent way inhibited...
The identification of new markers, the expression which defines phenotipically and functionally distinct cell subsets, is a main objective in biology. We have addressed issue identifying specific markers with reverse proteomic approach whereby approximately 1700 human open reading frames encoding proteins predicted to be transmembrane or secreted been selected silico for being poorly known, cloned expressed bacteria. These purified used immunize mice aim obtaining polyclonal antisera mostly...
Since its identification, HIV-1 remains a global health threat responsible for world-wide pandemic. The introduction of Anti-Retroviral Therapy (ART) greatly extended patients survival; however ART can control but not cure HIV infection. It has been recently suggested that by integrating near cancer-associated genes could promote the expansion and persistence infected cells in under ART. However, molecular mechanism/s insertional mutagenesis used physiological impact on harboring these...
Abstract High transduction rates of viral vectors in gene therapies (GT) and experimental hematopoiesis ensure a high frequency delivery, although multiple integration events can occur the same cell. Therefore, tracing sites (IS) leads to mis-quantification true clonal spectrum limits safety considerations GT. Hence, we use correlations between repeated measurements IS abundances estimate their mutual similarity identify clusters co-occurring IS, for which assume origin. We evaluate...
Genotoxicity assays based on systemic vector injection into newborn tumor-prone Cdkn2a−/− and Cdkn2a+/− mice has shown that self-inactivating (SIN) lentiviral (LV) harboring strong or moderate enhancer/promoters in internal position caused acceleration hematopoietic tumor onset compared to control mice. Integration site (IS) analysis vector-induced tumors showed oncogene activation suppressor inactivation occurs by mechanisms of aberrant splicing and/or enhancer-mediated overexpression...
The excellent therapeutic potential of self-inactivating (SIN) lentiviral vectors (LV) has been demonstrated in pre-clinical studies and clinical trials. However, weaker mechanisms insertional mutagenesis could endanger their applications. Systemic vector injection into newborn tumor-prone Cdkn2a-/- Cdkn2a+/-mice, conducted our previous work, that SINLVs harboring strong or moderate enhancer/promoters internal position caused acceleration hematopoietic tumor onset with respect to control...
It has been recently suggested that HIV-1 by integrating near cancer-associated genes could promote the expansion and persistence of infected cells in patients under Anti Retroviral Therapy (ART). However, molecular mechanism/s insertional mutagenesis used physiological impact on harboring these integrations are completely unknown. Here, we found peripheral blood mononuclear from 54 ART, BACH2 STAT5B were targeted a significant number compared to other lentiviral integration datasets...