A Phase 1 Study of Gene-modified Autologous Hematopoietic Stem Cell (BD211) Treating β-thalassemia Major

Inclusion Criteria:

1. Participants aged 3 years (inclusive) to 18 years (exclusive), with no genderrestrictions.

2. Parents/legal guardians have fully understood and voluntarily signed a writteninformed consent form; and it is recommended that children aged 8 and above beinvolved in the decision to participate in this clinical trial and obtain a writtenconsent form.

3. Transfusion-dependent β-thalassemia patients. "Transfusion-dependent" is defined as:requiring at least 100 mL/kg of packed red blood cells annually; the genotype can be β0/β0, β0/β+, or β+/β+, diagnosed through hemoglobin studies.

4. Eligible for allogeneic hematopoietic stem cell transplantation, but without a donoror those refusing to undergo allogeneic hematopoietic stem cell transplantation.

5. Have undergone symptomatic treatment for at least the past 2 years and have retainedmedical records including transfusion history.

6. Stable condition and maintained an appropriate iron chelation regimen.

7. Good status of organ function.

8. Good compliance from the individual and parents/legal guardians, willing to adhereto visit schedules, trial plans, laboratory tests, and other trial procedures asstipulated in this protocol.

9. Willing to participate in long-term follow-up research.

Exclusion Criteria:

1. Has a fully HLA-matched hematopoietic stem cell donor and is willing to receive afully HLA-matched hematopoietic stem cell transplant. Enrollment is otherwise onlyadvised after review by the safety review committee.

2. Positive for antibodies against Human Immunodeficiency Virus 1/2 (HIV-1/HIV-2),Treponema pallidum (TP) specific antibodies, Human T-lymphotropic Virus 1 or 2 (HTLV-1/HTLV-2) antibodies, and Vesicular Stomatitis Virus G (VSV-G).

3. Positive for Hepatitis B Virus (HBV) HbsAg or HBV-DNA; Hepatitis C Virus (HCV) HCAbpositive; positive nucleic acid test for Epstein-Barr Virus (EBV) or Cytomegalovirus (CMV).

4. Severe active bacterial, viral, fungal, malarial, or parasitic infections.

5. Has had, or currently has, a malignant, myeloproliferative, or immunodeficiencydisorder.

6. Direct relatives with known or suspected hereditary cancer syndromes (including butnot limited to breast cancer, colorectal cancer, ovarian cancer, prostate cancer,and pancreatic cancer).

7. Autoimmune diseases that could result in transfusion difficulties.

8. Major organ diseases or abnormal lab tests, including:

9. Liver cirrhosis, fibrosis, or active hepatitis, and/or abnormal liver functiontests (Serum total bilirubin (TBIL) ≥ 1.5x Upper Limit of Normal (ULN); Alanineaminotransferase (ALT) and Aspartate aminotransferase (AST) ≥ 2.5x ULN;Alkaline phosphatase ≥ 2.5x ULN).

10. Heart disease, or Left Ventricular Ejection Fraction (LVEF) < 60%.

11. Kidney diseases, or serum creatinine ≥ 1.5ULN, creatinine clearance rate < 30%of the normal level (measured or calculated by the Cockcroft-Gault equation).

12. Endocrine disorders, such as insulin-dependent diabetes, hyperthyroidism, orhypothyroidism.

13. Severe iron overload, serum ferritin ≥ 5000 ng/mL.

14. Cardiac T2* < 20 ms, and/or liver iron content (LIC) ≥ 15mg/g liver weight byMRI.

15. Significant pulmonary hypertension diagnosed clinically according toguidelines, requiring clinical medical intervention.

16. Uncorrected bleeding disorders.

17. Severe psychiatric disorders.

18. Peripheral blood white cell (WBC) count < 3x10^9/L or platelets count < 120x10^9/L.

19. Received hydroxyurea treatment within the last 3 months before stem cell collection.

20. Used erythropoiesis-stimulating agents within the 3 months prior to HSC collection.

21. History of allogeneic transplantation.

22. Previously received any type of gene and/or cell therapy.

23. Participating in another clinical trial and is within a 30-day screening period.

24. Has contraindications to anesthesia.

25. Has contraindications to hematopoietic stem cell collection.

26. Allergic to the investigational drug or its excipients.

27. Any other conditions determined by the investigator as unsuitable for participationin this clinical trial.