Regenerative Medicine and Gene Therapy

Giovanni Sorrentino, Head of Molecular Liver Pathophysiology Unit Department of Life Sciences – University of Trieste Trieste, ITALY speaks on "New avenues in disease modeling and regenerative medicine of the enterohepatic system".

Shyni Varghese, Professor & MEDx Investigator, Department of Biomedical Engineering, Mechanical Engineering and Materials Science Department of Orthopaedic Surgery, Pratt School of Engineering & Duke Medical Center, Durham, NC USA speaks on "Physicochemical properties of extracellular matrix: Key to function, Clue to mechanism". This movie has been recorded at ICGEB Trieste.

Nadja Ring completed her masters in Human biology at the Philipps University of Marburg, Germany, with a focus on molecular biology and genetics. Her passion for translational research and using science to improve health and wellbeing brought her to ICGEB, Trieste for her PhD in molecular biology. Here, Nadja Ring used high throughput screening to identify microRNAs able to combat cellular senescence, in the search of possible biotherapeutics to be used in aging related diseases. In her current position as a postdoctoral fellow in the group of Serena Zacchigna in ICGEB, Nadja Ring has continued to use high throughput screening to identify therapeutic solutions for a range of diseases, while also supervising PhD projects and being in charge of screening facility use for the group. Her main project is a transdisciplinary approach combining high throughput screening data with collaborations in machine learning and chemical compound synthesis. This has led to the identification of a novel compound which acts as a powerful anti-fibrotic drug in a mouse model of lung fibrosis. In addition to research, Nadja Ring also seeks to foster science diplomacy, by contributing to interregional projects, international workshops and outreach programs.

Lutz Hein, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Germany speaks on "Dynamics of the epigenome in cardiac myocyte development and disease". This movie has been recorded at ICGEB Trieste.

Shuo Lin, Biozentrum, University of Basel, Basel, SWITZERLAND speaks on "Designed linker proteins restore basement membrane and correct LAMA2-related muscular dystrophy". This movie has been recorded at ICGEB Trieste.

Jesus Gil, Cell Proliferation Group MRC London Institute of Medical Sciences (LMS) Imperial College, Hammersmith Hospital Campus London, UK speaks on "Linking senescence and inflammation: the senescence-associated secretory phenotype (SASP)". This movie has been recorded at ICGEB Trieste.

Eduard Ayuso, INSERM 1089, University of Nantes, Nantes, France speaks on "Unraveling mechanisms and biology of recombinant AAV vectors

produced in insect cells". Recombinant adeno-associated vectors (rAAV) are viral vectors of choice for gene therapy of many inherited diseases. Medicinal products based on rAAV are predominantly manufactured by transient transfection of mammalian cells or baculovirus expressing vectors (BEV) infection of insect cells, being the latter method more suitable for large-scale production. Although AAVs are mammalian viruses they can be assembled in insect cells, but the biology of the system has been poorly investigated. Here, we have studied the role of the assembly-activating protein (AAP) in insect cells and we found that this protein is expressed in a similar manner as in mammalian cells. By knocking down the AAP, it was confirmed that AAP is required for the assembly of AAV2 particles in insect cells. Next, we aimed to identify and characterize DNA species encapsidated in rAAV stocks produced in insect cells. To this end, we developed a single-strand virus sequencing protocol based on Illumina high-throughput sequencing technology (HTS). Preliminary data obtained from rAAV stocks puri ed by CsCl ultracentrifugation or immunoaffnity chromatography revealed that baculoviral and cellular DNA correspond to ≤1.5% and ≤0.02% of the total reads, respectively. Moreover, the sequencing coverage showed that the proximity to the ITRs increases progressively the probability for baculoviral DNA to be encapsidated. Nonetheless, these baculovirus-derived reads are found at a frequency of 2-3 logs lower than the rAAV genome reads. The development of accurate quality control methods is not only critical for fulfilling regulatory requirements, but will also provide novel insights into the biological mechanism of rAAV assembly in insect cells. This movie has been recorded by ICGEB Trieste.

Fulvio MAVILIO, Genethon, Evry - FRANCE speaks on "Gene Therapy of Inherited Neuromuscular Diseases". This seminar has been recorded by ICGEB Trieste

Adi BARZEL, Founder and Chief Scientific Officer of LogicBio Therapeutics Inc. Tel Aviv - ISRAEL speaks on "Therapeutic levels of in vivo gene targeting without nucleases”. This seminar has been recorded by ICGEB Trieste

Paolo Bianco Sapienza University of Rome, Rome - ITALY speaks on "Skeletal stem cells and the stromal system: moving away from the "mesenchymal" conceptual bug". This seminar has been recorded by ICGEB Trieste