Safety and Efficacy of Gene Modified Autologous Hematopoietic Stem Cells to Treat Transfusion-dependent Beta-thalassemia

Inclusion Criteria:

1. Ages 3 to 18 years old, including: The parents or legal guardians must be able to understand and provide ICFs. Ifavailable, it is strongly recommended that children aged ≥8 years in treatmentdecisions and obtain written ICFs and be clearly documented; Diagnosed asTransfusion Dependent β-thalassemia with any genotype (β0, β+, βE/β0, βS/S, βS/β0, βS/β+), confirmed the Hb analysis. No alfa chain genetic abnormalities. Subjectsmust stabilize and maintain an appropriate iron chelation regimen.Transfusion-dependent types are defined as requiring at least 100 mL/kg/ year of redblood cells (pRBCs).

2. No eligiblity for allogeneic hematopoietic stem cell transplantation.

3. The treatment of erythrocyte maturation agent luspatercept cannot be financiallysupported.

4. The subjects' parents/legal guardians must be willing and able to follow the studyprocedures in the study protocol.

5. Good organs' functions.

6. Having complete medical records including a history of blood transfusions testifiedsubject received treatment and followed up for at least two years prior to screening .

Exclusion Criteria:

1. Availability of voluntary, fully HLA-matched hematopoietic cell donors, unlessrecommended for inclusion by the Monitoring Committee.

2. HIV-1 and HIV-2 were positive, and / or HTLV-1, HTLV-2 and VSV-G antibodies werepositive.

3. An active bacterial, viral, fungal or parasitic infection.

4. Contraindicated for the extraction of bone marrow under anesthesia.

5. Any malignancy, myeloproliferative, or immunodeficient disease and relevant medicalhistory.

6. Peripheral blood white blood cell (WBC) count < 3×10^9/L or platelet count < 120×10^9/L.

7. A history of allo-transplantation.

8. Erythropoietin was used within 3 months prior to HSC cell collection.

9. Immediate family members with known or suspected familial cancer syndromes (including but not limited to breast, colorectal, ovarian, prostate, and pancreaticcancers).

10. Subjects with a diagnosis of major mental illness may had a serious disability toparticipate in the study.

11. Active recurrent malaria.

12. Had autoimmune diseases that may make blood transfusions difficult.

13. History of major organ injury including: Liver disease, transaminase > 3 times the upper limit of normal. (If the liverbiopsy does not reveal evidence of widespread bridging fibrosis, cirrhosis, or acutehepatitis, this indicator will not be used as a criterion for the exclusion); Widelybridging fibrosis, histopathological evidence of acute hepatitis or cirrhosis showedin liver biopsy Heart disease, left ventricular ejection fraction < 25%; Kidneydisease, creatinine clearance < 30% normal level; Of severe iron overload, confirmedby the study doctor; An heart MRI detection of T2 * < 10 ms; Significant pulmonaryhypertension needing clinical medical intervention.

14. There are bleeding diseases that have not been cured.

15. The subject involved with another clinical study in a 30-day screening period.

16. Allergic to the research drug and its excipients.

17. Prior treatment with any type of gene and/or cell therapy.

18. As assessed by the investigator, the subjects or their parents are unable to complywell with the study procedures per protocol.

19. Hydroxyurea treatment within 3 months prior to hematopoietic stem cell collection.

20. Had diseases that interfere with hematopoietic stem cells collections.

21. Any other conditions being ineligible for HSC transplantation determined by theinvestigator.