Safety and Efficacy Evaluation of Autologous CRISPR-Cas12b Edited Hematopoietic Stem Cells

Inclusion Criteria:

• Age 3-35 years old (inclusive), male or female;
• The subject and/or his/her legally recognized representative/parent/guardian fullyunderstands the study and all information related to the study and has signed theinformed consent form;
• Clinical diagnosis of transfusion-dependent β-thalassemia (TDT) with a bloodtransfusion record within 2 years (inclusive) prior to screening showing a history of ≥ 10 units (U)/kg/year (or ≥ 100 mL/kg/year) or ≥ 8 times/year of suspended RBCtransfusions in at least 1 consecutive 12-month period;
• Karnofsky score (for subjects aged ≥ 16 years) or Lansky score (for subjects aged < 16years) of ≥ 80;
• Subjects in stable disease state who are eligible for hematopoietic stem celltransplantation as per investigator's judgment;
• Access to diagnosis and treatment records issued by medical professional institutionswithin 2 years prior to screening, including the records of blood transfusions,hematology, serum chemistry, and other examinations;
• Willing and able to comply with study procedures, with good compliance, and willing toreceive and complete the follow-up study with a duration of at least 2 years;
• Subjects of childbearing potential (including female subjects of childbearingpotential and male subjects whose partners are of childbearing potential) must useeffective contraception within 12 months of treatment.

Exclusion Criteria:

• Diagnosis of associated α-thalassemia: > 1 alpha chain deletion or alpha genefunctional defect;
• Have available HLA-fully matched donors and acceptable for allogeneic hematopoieticstem cell transplantation;
• Irregular antibody or platelet antibody positive;
• Prior allogeneic bone marrow transplantation or gene therapy;
• Subjects with clinically significant and active bacterial, viral, fungal, or parasiticinfection as determined by the investigator at screening, including but not limited tothose with positive etiology of human immunodeficiency virus (HIV-1/2), humancytomegalovirus (HCMV-DNA), Epstein-Barr virus (EBV-DNA), or Treponema pallidumantibody (TP-Ab), or with previous hepatitis B or C infection;
• Subjects with an injury of major organs
• Contraindications for hematopoietic stem cell collection and poor collectionefficiency judged by the investigator;
• Contraindications to the clinical investigational product and its excipients, G-CSF (hematopoietic stem cell mobilization), plerixafor (hematopoietic stem cellmobilization), busulfan (myeloablation), and other drugs;
• Participation within 3 months prior to screening or current participation in anotherinterventional clinical study;
• History or family history of malignancy or myeloproliferative disorder;
• History of uncontrollable epilepsy, mental disorder, or other psychiatric disorders;
• Abuse of psychoactive substance, drug, or alcohol within 6 months prior to enrollment;
• Pregnant or breastfeeding females;
• Other diseases or reasons that interfere with study procedures;
• Any other conditions that the investigator deems unsuitable for the subject'sparticipation in the study.