San Raffaele Telethon Institute for Gene Therapy
The San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) was created in 1995 as a joint venture between the Telethon Foundation and IRCCS Ospedale San Raffaele, with the mission to perform cutting-edge research in gene and cell therapy and to translate its results into therapeutic advances, focusing on genetic diseases.
Overall, SR-Tiget represents a multi-disciplinary research environment, which provides a unique blend of scientific expertise in the development of innovative gene and cell therapy strategies, access to relevant preclinical models to evaluate their efficacy and safety, as well as competence in conducting early phase clinical trials. This provides a fertile ground for alliances with industrial partners, which possess the skills and resources required to address the regulatory hurdles and manufacturing needs to bring new therapies to registration and make them available to patients.
View all the research units here.
Research at SR-Tiget spans from basic research to pre-clinical studies to early phase clinical trials according to the following major aims:
- identifying the genetic bases and the pathophysiological processes underlying several types of inherited diseases, including primary immunodeficiencies and autoimmune/autoinflammatory diseases, hematologic diseases, inherited leukodystrophies and other lysosomal storage and neurodegenerative diseases;
- developing novel ex vivo or in vivo gene and cell therapy strategies for such diseases and validating them in ad hoc designed experimental models;
- ameliorating the performance and safety of gene transfer employed for these therapies, i.e. by stringently targeting transduction or expression of lentiviral vectors to the desired cell types and reducing their impact on endogenous transcription at genomic insertion sites;
- characterizing the biological properties of hematopoietic and neural stem and progenitor cells and of mesenchymal stromal cells targeted by these therapies and improving the procedures for their ex vivo isolation, genetic modification and transplantation;
- developing novel technological platforms, including targeted genome and epigenome editing using artificial enzymes with DNA sequence-specific activity (such as ZFN, TALEN and CRISPR-Cas9 nucleases) and scaffolds for ex vivo organoid culture (e.g. for hematopoietic stem cell niche reconstitution);
- investigating the cell types that mediate innate and adaptive immunity, with the aim to develop strategies to induce immunological tolerance to gene and cell products, in order to improve the efficacy and stability of such therapies;
- exploiting the platforms and strategies developed through the abovementioned investigations to design new gene and cell therapies for some common diseases, i.e. to induce tolerance in diabetes and other autoimmune diseases or, conversely, enhance adaptive immunity to cancer associated antigens.
SR-Tiget portfolio of gene and cell therapies now embraces the full spectrum of drug development up to the market. Notably, in May 2016 the European Commission granted marketing authorization for Strimvelis for the treatment of ADA-SCID, a severe form of immunodeficiency. Strimvelis, which is the first approved ex vivo gene therapy worldwide, has been developed at SR-Tiget and brought to the market under a strategic alliance with GSK. The successful results obtained with ADA-SCID provided a rationale for extending the HSC gene therapy approach to other diseases. In particular, two clinical trials for Wiskott-Aldrich Syndrome (WAS) and Metachromatic Leukodystrophy (MLD) started in 2010 and have shown persistent therapeutic benefit in the absence of treatment-related adverse events. A third trial, for beta‐thalassemia, started in 2015 and is showing promising preliminary results. In addition, a trial for Mucopolysaccharidosis type I (MPS-I) is planned to start in 2018.
The CLINICAL RESEARCH Units of SR-Tiget work in close collaboration with the Stem Cell Program and the Pediatric Immuno-Hematology Unit of IRCCS Ospedale San Raffaele.
To foster the development from bench to bedside of the new therapeutic strategies being investigated at SR-Tiget, the following structures have been established in the Institute:
First academic GLP center for performing biodistribution, toxicology/tumorigenicity and validation studies on gene and cell therapy products. The facility was certified by the Italian Ministry of Health in March 2014 and renewed in April 2016.
2. Vector Integration Core
Performs genome-wide profiling of vector integration sites as readout of cell growth at clonal level, in basic research studies and technology development, in preclinical safety studies and in gene therapy treated patients.
3. GCLP (Good Clinical Laboratory Practices) Laboratory
To ensure data integrity and reliability in analyses of samples from clinical trials.
4. Process Development Laboratory (in preparation)
To develop new protocols for vector production, gene editing and ex vivo cell manipulation in a context of GSP (Good Scientific Practices) and Quality by Design.
Clinical research Unit
Focused on the application of basic research discoveries and innovative gene and cell therapy approaches to the treatment of genetic diseases
Gene and neural stem cell therapy for lysosomal storage diseases
Focused on mechanisms and novel gene therapy approaches for lysosomal storage diseases
Gene transfer into stem cell
Focused on the field of hematopoietic stem cell biology and gene transfer to treat genetic diseases, such as beta-thalassemia
Gene transfer technology and new gene therapy strategies
Developing platforms for safe and efficient gene transfer, mostly based on modified viruses, and for targeted gene editing
Genomics of the innate immune system
Aim to decipher the complex networks of signaling pathways, transcription factors, chromatin regulators and non-coding RNAs that control gene expression in the innate immune system
Human hematopoietic development and disease modeling
Understanding normal and pathological human hematopoietic development, both at the signaling and genetic level
Mechanisms of peripheral tolerance
Focused on the molecular and cellular mechanisms controlling immune tolerance, tissue homeostasis and adverse immune responses
Pathogenesis and treatment of immune and bone diseases
Focused on genetic defects characterised by infections and autoimmunity, and their therapeutic approach
Pathogenesis and therapy of primary immunodeficiencies
Focused on the identification of the genetic bases and the pathophysiological processes underlying PIDs and autoimmune/autoinflammatory diseases
Translational stem cell and leukemia
Operating at the intersection of science and clinics, with the mission to bring cutting edge science to patients, in particular with acute leukemia
Retrovirus-host interactions and innate immunity to gene transfer
Focused on molecular mechanisms of host-vector interplay and innate immunity in the context hematopoietic stem cell (HSC) gene therapy
Senescence in stem cell aging, differentiation and cancer
Identifying molecular determinants of human aged and stressed hematopoiesis, focusing on cell mechanisms of stem cell aging
Head, Gene transfer technologies and new gene therapy strategies Unit
Head, Pathogenesis and therapy of primary immunodeficiencies Unit
Group leader, Translational stem cell and leukemia Unit
Raffaella Di Micco
Group leader, Senescence in stem cell aging, differentiation and cancer Unit
Group leader, Human hematopoietic development and disease modeling Unit
Head, Gene transfer into stem cell Unit
Group leader, Mechanisms of peripheral tolerance Unit
Head, Gene and neural stem cell therapy for lysosomal storage diseases Unit
Group leader, Retrovirus-host interactions and innate immunity to gene transfer Unit
Group leader, Genomics of the innate immune system Unit
Head, Pathogenesis and treatment of immune and bone diseases Unit
We are looking for highly motivated scientists to be enrolled as Postdoctoral Fellows in the research unit "Genomics of the innate immune system", headed by ERC Starting Grantee Renato Ostuni, at San Raffaele Telethon Institute for Gene Therapy
A post-doctoral fellowship is immediately available at the Mechanisms of Peripheral Tolerance Unit at the San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), headed by Silvia Gregori
Postdoctoral Fellow, Research Fellow and PhD candidate positions are available in the Human hematopoietic development and disease modeling unit, headed by Dr. Andrea Ditadi, at the SR-TIGET
A technician position is available in th Pathogenesis and therapy of primary immunodeficiencies unit, headed by professor Alessandro Aiuti
We are looking for a candidate for the role of Scientific Officer of SR-TIGET reporting to the Director of Institute
We are currently looking for a person to fill the double role of Alliance Manager and Regulatory Affairs Officer