European Commission logo
English English
CORDIS - EU research results

Towards Safe and Effective Hematopoietic Stem Cell Gene Therapy: Targeting Integration to Genomic Safe Harbors and Exploiting Endogenous microRNA to Regulate Transgene Expression


Hematopoietic stem cell gene therapy has a tremendous potential to treat human disease. Yet, in conjunction with the first successful results in the clinic, severe adverse events linked to the gene transfer protocol were reported. Recently, we provided proof-of-principle of two new powerful strategies to improve the efficacy and safety of gene transfer: 1) regulating transgene expression by exploiting cellular microRNAs; 2) targeting integration at predetermined sites of the genome by forcing homologous recombination with designer Zinc finger nucleases. Here we will investigate the microRNA network regulating hematopoiesis and exploit the new knowledge to develop vectors with stringently controlled expression throughout the hematopoietic lineages. We will develop Zinc finger nuclease-based vectors that insert the transgene with high efficiency and specificity either downstream to its own endogenous promoter or into a safe genomic harbor that allows for robust expression without interference on the neighboring genes. By combining these strategies we will provide radically improved gene transfer platforms. Furthermore, we will exploit these technologies for the generation and genetic correction of induced pluripotent stem cells, providing a potentially unlimited source of patient-derived vector free gene corrected multipotent stem cells for future applications of regenerative medicine. The new gene therapy strategies will be tested in pre-clinical models of leukodystrophies and immunodeficiencies, for which we have extensive experience, and should enter a clinical trial for at least one such disease by the end of the proposed funding period. If successfully validated, the new strategies may eventually broaden the scope of gene therapy in medicine.

Call for proposal

See other projects for this call

Host institution

EU contribution
€ 910 800,00
20132 Milano

See on map

Nord-Ovest Lombardia Milano
Activity type
Higher or Secondary Education Establishments
Principal investigator
Luigi Naldini (Prof.)
Administrative Contact
Maria Rosa Pedrazzi (Dr.)
Total cost
No data

Beneficiaries (3)