
San Raffaele Telethon Institute for Gene Therapy
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.
Download here the brochure.
Basic Research
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.
Clinical research
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:
1. GLP (Good Laboratory Practices) Test Facility
First academic GLP Test Facility for performing biodistribution, toxicology/tumorigenicity and validation studies on gene and cell therapy products. Certified by the Italian Ministry of Health in March 2014; renewed in April 2016 and 2018.
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. SR-Tiget clinical Lab
Performs analytical tests of samples from patients enrolled in clinical protocols, including Phase I clinical trials according to the minimum requirements of Determine AIFA 809/2015 and Good Clinical Laboratory Practice (GCLP) standards and in compliance with Good Clinical Practices (GCP).
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.
5. Bioinformatics core
Alessandro Aiuti
Group leader, Pathogenesis and therapy of primary immunodeficiencies Unit
Alessio Cantore
Group leader, Liver gene therapy Unit
Raffaella Di Micco
Group leader, Senescence in stem cell aging, differentiation and cancer Unit
Andrea Ditadi
Group leader, Human hematopoietic development and disease modeling Unit
Giuliana Ferrari
Group leader, Gene transfer into stem cell Unit
Bernhard Gentner
Group leader, Translational stem cell and leukemia Unit
Silvia Gregori
Group leader, Mechanisms of peripheral tolerance Unit
Angela Gritti
Group leader, Gene and neural stem cell therapy for lysosomal storage diseases Unit
Anna Kajaste-Rudnitski
Group leader, Retrovirus-host interactions and innate immunity to gene transfer Unit
Angelo Lombardo
Group leader, Epigenetic regulation and targeted genome editing Unit
Eugenio Montini
Group leader, Safety of gene therapy and insertional mutagenesis Unit
Luigi Naldini
Group leader, Gene transfer technologies and new gene therapy strategies Unit
Renato Ostuni
Group leader, Genomics of the innate immune system Unit
Anna Villa
Group leader, Pathogenesis and treatment of immune and bone diseases Unit
Research assistant position at Immune Core at SR-Tiget
We are looking for a researcher who will help develop new techniques and assays to integrate stem cell biology, immunology and developmental biology
A Postdoctoral position is available at SR-Tiget in the Epigenetic regulation and targeted genome editing Unit, headed by Angelo Lombardo
A post-doctoral fellow position is available in the Retrovirus-Host Interactions and Innate Immunity to Gene Transfer unit of the San Raffaele Telethon Institute for Gene Therapy
A Staff Scientist position is immediately available in the Process Development Laboratory at the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Milan, Italy