Gene Therapy for Pyruvate Kinase Deficiency (PKD): A Phase I Clinical Trial to Evaluate the Safety of the Infusion of Autologous CD34+ Cells Transduced with a Lentiviral Vector Carrying the Codon Optimized Red Cell Pyruvate Kinase (coRPK) Gene in Adult and Pediatric Subjects with PKD

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• 1. Presence of other known causes of hemolysis (in addition to PKD). Patients with concurrent G6PD deficiency diagnosed during pre-study evaluation may be considered for eligibility if in the opinion of the Investigator, the hemolytic anemia is the result of PKD and the G6PD deficiency is considered an incidental finding. 2. A venous thromboembolic event (VTE; i.e., pulmonary embolism or deep vein thrombosis) or arteriothromboembolic event (ATE; including unstable angina, myocardial infarction, stroke or transient ischemic attack) during the prior 12 months. 3. Any evidence of severe iron overload that, per Investigator discretion, warrants exclusion. 4. Evidence of bridging fibrosis, cirrhosis or active hepatitis on liver biopsy. Liver biopsy is required when liver iron concentration (LIC) is ≥ 15 mg/g on T2* magnetic resonance imaging (MRI) of liver. If a liver biopsy has been performed less than 6 months prior to enrollment, it does not need to be repeated. 5. Significant medical conditions including documented HIV infection, active viral hepatitis, poorly-controlled hypertension, pulmonary hypertension, cardiac arrhythmia or congestive heart failure; or ATEs (including stroke or myocardial infarction) within the 6 prior months. 6. Active hematologic or solid organ malignancy, not including nonmelanoma skin cancer or another carcinoma in situ. Patients with previously resected solid organ malignancies or definitively treated hematologic malignancies may be eligible if there has been no evidence of active malignancy during the prior 3 years. 7. Uncontrolled seizure disorder. 8. Cardiac T2* <10 ms by magnetic resonance imaging (MRI) or left ventricular ejection fraction (LVEF) <45% by echocardiogram or multiple gated acquisition scan (MUGA). 9. Hepatic dysfunction as defined by: • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 × the upper limit of normal (ULN). 10. Renal dysfunction defined as serum creatinine >ULN. Patients with creatinine above ULN may be eligible pending documentation of a glomerular filtration rate ≥ 60 mL/min/1.73m2 as calculated by Modification of Diet in Renal Disease equation, the revised Schwartz formula (for patients under 18 years old), or 24-hour urine collection. 11. Pulmonary dysfunction as defined by either: • Need for supplemental oxygen during the prior 2 weeks (in absence of acute infection) or • Oxygen saturation (by pulse oximetry) <90%. 12. Any medical or other contraindication for leukapheresis as determined by the treating Investigator. 13. Any medical or psychiatric condition that in the opinion of the Investigator renders the patient unfit for trial participation or at higher than acceptable risk for participation. 14. Poor functional status, evidenced by Karnofsky Index <70 in adults or Lansky <70 in children. 15. Participation in another clinical trial with an investigational drug within 14 days before the informed consent signature. Participation in observational studies is allowed. 16. Pregnant women or women with a positive serum pregnancy test at screening or breast feeding or planning to become pregnant within the next 24 months. Women not willing to use highly effective contraceptive methods during the complete study period.* 17. Previous allogeneic or other hematopoietic stem cell transplant * Females of childbearing age potential and male patients with partners of childbearing potential must use highly effective contraceptive measures (according to Clinical Trials Facilitation Group recommendations).