It is a single-arm, single-center, open-label, single-dose study. A total of three subjects with severe sickle cell disease (SCD), aged 12-50 years (inclusive), are planned to receive cell infusion. After successful hematopoietic stem cell engraftment is achieved in the first subject, cell infusion will be initiated for subsequent subjects.

Inclusion Criteria:

• 12-50 years of age (inclusive) at the time of screening
• Diagnosed with sickle cell disease (SCD) with a βS/βS, βS/β0 or βS/β+ genotype.
• Experienced at least 4 severe vaso-occlusive events (VOEs) in the two years before informed consent, despite supportive care measures (e.g., a pain management plan).
• Have a Karnofsky Performance Status (KPS) score (for subjects ≥16 years) or Lansky Performance Status (LPS) score (for subjects <16 years) of ≥60.
• Have experienced either hydroxyurea (HU) failure at any time in the past or demonstrated intolerance to HU.
• Subject must have been treated and followed for at least two years before informed consent at the medical center that maintained detailed records of their sickle cell disease history.
• Be willing and able to comply with all study procedures and visit schedules.
• The subject and/or their legally authorized representative must voluntarily agree to participate, sign the informed consent form, and be capable of completing all follow-up assessments required by the protocol.

Exclusion Criteria:

• Have any severe active infection (fungal, bacterial, viral, tuberculosis, or other), including active Hepatitis B (defined as serum HBV-DNA ≥2000 IU/mL), active Hepatitis C virus (HCV) infection, positive human immunodeficiency virus (HIV) antibody, or active syphilis.
• Inadequate bone marrow function, as defined by an absolute neutrophil count of <1.0 x 10^9/L (<0.5 x 10^9/L for subjects on hydroxyurea treatment) or a platelet count <100 x 10^9/L.
• Have severe cerebrovascular disease, including a history of significant ischemic or hemorrhagic stroke, abnormal Transcranial Doppler (TCD) flow velocities requiring chronic transfusion therapy (>200 cm/s), occlusion or stenosis of the circle of Willis, or any history of moyamoya disease.
• Baseline oxygen saturation < 90% without supplemental oxygen (excluding periods of SCD crisis, severe anemia or infection).
• Baseline carbon monoxide diffusing capacity (DLCO) < 50% (corrected for Hb) in the absence of infection. If DLCO cannot be assessed due to age or cognitive limitations, there must be a normal respiratory exam, a chest radiograph without pulmonary infiltrates, and oxygen saturation by pulse oximetry ≥ 90% on room air.
• Baseline left ventricular ejection fraction (LVEF) < 45%
• Clinically significant pulmonary hypertension at baseline, as defined by the requirement for ongoing pharmacologic treatment or the consistent or intermittent use of supplemental oxygen.
• Baseline estimated glomerular filtration rate (eGFR) <70 mL/min/1.73 m^2
• Advanced liver disease
• Have a definite contraindication to stem cell collection.
• Have any prior or current malignancy, myeloproliferative disorder, or immunodeficiency disease.
• Have white blood count <3.0 x 10^9/L and/or platelet count <100.0 x 10^9/L not due to hypersplenism.
• Have a diagnosis of compound alpha-thalassemia (excluding silent carrier).
• Have significant iron overload at screening, defined as severe iron overload on liver MRI, or serum ferritin levels >2000 ng/mL, or cardiac T2* <10 ms.
• Have positive irregular red cell antibodies or platelet antibodies.
• Be eligible for allogeneic hematopoietic stem cell transplantation and have an identified willing, fully HLA-matched donor.
• Prior receipt of gene therapy or allogeneic hematopoietic stem cell transplantation.
• Immediate family member with a known or suspected Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary non-polyposis colorectal cancer syndrome, and familial adenomatous polyposis).
• Have a diagnosed major psychiatric disorder or predisposition that, in the Investigator's opinion, would severely compromise the ability to participate in the clinical study.
• Have an uncorrectable coagulation disorder or a history of severe hemorrhagic disease.
• Have any other condition that, in the opinion of the treating physician, renders the subject unsuitable for hematopoietic stem cell transplantation.
• Have a known allergy to the investigational drug(s) (e.g., plerixafor, busulfan) or their components.
• Have participated in or are currently participating in another interventional clinical study within 3 months before screening.
• Received a live vaccine within 6 weeks before screening.
• Be pregnant or breastfeeding.
• The subject or their partner is unwilling to use medically acceptable effective contraception during the 32-month study period.
• Unable to receive red blood cell transfusion.
• The subject or their parent/guardian is unable to adhere to the study protocol.
• Have any other condition deemed by the Investigator to make the subject unsuitable for participation in this study.