Inclusion Criteria: * Written informed consent * Transfusion-dependent beta-thalassemia (any genotype). Transfusion dependence is defined as receiving ≥ 8 transfusions of blood per year over a minimum of 2 years. * Karnofsky Index or Lansky \> 80% * Age ≥ 3 years and \< 65 years * Adequate cardiac, renal, hepatic and pulmonary functions as evidenced by: * Left ventricular ejection fraction (LVEF) greater than 45% by echo and normal ECG or presence of abnormalities not significant for cardiac disease. Absence of severe pulmonary hypertension * Diffusing capacity of the lung for carbon monoxide (DLCO) \> 50% and forced expiratory volume in 1 sec (FEV1) and forced expiratory vital capacity (FVC) \> 60% predicted (if non cooperative: pulse oximetry \> 95 % in room air) * Serum creatinine \< 1.5 upper limit of normal * Absent-mild-moderate liver iron overload on T2\*MRI (less than 12 months before enrolment) * Absent-mild-moderate cardiac iron overload T2\*MRI (less than 12 months before enrolment) * Absence of severe liver fibrosis or cirrhosis on fibroscan or liver biopsy (less than 12 months before enrolment) * Low risk thrombophilic screen and negative history of significant previous thrombotic events * For all patients in reproductive age, agreement to use highly effective and adequate method of contraception while receiving treatment phase and for at least 12 months following drugs administration (including both females of child bearing potential and males with partners of child bearing potential) * Good adherence to transfusion and chelation programme as indirect evidence of good adherence to treatment and follow-up evaluations for current trial * Availability of an adequate and well documented transfusion history (at least previous 6 months) or availability to follow a regular transfusion regimen according to guidelines and provide a detailed transfusion record of the 6 months prior to intervention phase Exclusion Criteria: * Use of other investigational agents within 4 weeks prior to study enrolment (within 6 weeks if use of long-acting agents) * Severe, active viral, bacterial, or fungal infection at eligibility evaluation * Malignant neoplasia (except local skin cancer or cervical intraepithelial neoplasia) or exceptional family history of familial cancer syndromes * Myelodysplasia, cytogenetic alterations associated with neoplasia, or other serious haematological disorder than thalassemia * History of uncontrolled seizures * Other clinical conditions judged non compatible with the procedure and/or the treatment * Positivity for HIV (serology or RNA), and/or HbsAg and/or HBV DNA and/or HCV RNA (or negative HCV RNA but on antiviral treatment) and/or Treponema Pallidum or Mycoplasma active infection * Active alcohol or substance abuse within 6 months of the study * Pregnancy or lactation * Previous allogeneic bone marrow transplantation or gene therapy * For paediatric patients only: availability of an HLA-matched donor (sibling or of a suitable 10/10 matched unrelated donor).