Approved and Successful Gene Therapies

1. Spinal Muscular Atrophy (SMA)

• Zolgensma (onasemnogene abeparvovec)

  • Company: Novartis

  • Mechanism: AAV9 vector delivers SMN1 gene

  • Approved by: FDA (2019), EMA, others

  • Target: Infants with SMA Type 1

  • Outcome: Dramatic improvement in motor function and survival

2. Inherited Retinal Disease

• Luxturna (voretigene neparvovec)

  • Company: Spark Therapeutics (Roche)

  • Mechanism: AAV2 vector delivers functional RPE65 gene

  • Approved by: FDA (2017), EMA

  • Target: RPE65-mediated retinal dystrophy

  • Outcome: Improved vision in treated patients

3. Beta-Thalassemia

• Zynteglo (betibeglogene autotemcel)

  • Company: bluebird bio

  • Mechanism: Lentiviral vector introduces functional HBB gene into stem cells

  • Approved by: EMA (2019), FDA (2022)

  • Target: Transfusion-dependent beta-thalassemia

  • Outcome: Transfusion independence in most patients

4. Sickle Cell Disease

• Casgevy (exa-cel; formerly CTX001)

  • Companies: Vertex + CRISPR Therapeutics

  • Mechanism: CRISPR-Cas9 edits BCL11A enhancer to boost fetal hemoglobin

  • Approved by: FDA (2023), UK MHRA

  • Outcome: Elimination or dramatic reduction in vaso-occlusive crises

• Lyfgenia (lovotibeglogene autotemcel, or lovo-cel)

  • Company: bluebird bio

  • Mechanism: Lentiviral vector expressing anti-sickling hemoglobin

  • Approved by: FDA (2023)

  • Outcome: Clinically meaningful reduction in pain events

5. Hemophilia A

• Roctavian (valoctocogene roxaparvovec)

  • Company: BioMarin

  • Mechanism: AAV5 vector delivers Factor VIII gene

  • Approved by: EMA (2022), FDA (2023)

  • Outcome: Reduced bleeding events and need for infusions

6. Hemophilia B

• Hemgenix (etranacogene dezaparvovec)

  • Company: CSL Behring/uniQure

  • Mechanism: AAV5 vector delivers Factor IX gene

  • Approved by: FDA (2022), EMA (2023)

  • Outcome: Sustained FIX levels and reduced bleeding

7. Metachromatic Leukodystrophy (MLD)

• Libmeldy (atidarsagene autotemcel)

  • Company: Orchard Therapeutics

  • Mechanism: Lentiviral vector delivers ARSA gene into autologous stem cells

  • Approved by: EMA (2020) FDA (2024)

  • Outcome: Prevention of neurological decline in pre-symptomatic children

8. ADA-SCID (Adenosine Deaminase Severe Combined Immunodeficiency)

• Strimvelis

  • Company: Orchard Therapeutics

  • Mechanism: Retroviral vector with ADA gene in autologous stem cells

  • Approved by: EMA (2016)

  • Outcome: Functional immune system restoration