This is a Phase 1b, Multicenter, Open-Label, Dose Finding Study to Investigate the Safety and Tolerability of a Single Intravenous Dose of SGT-501 in participants with catecholaminergic polymorphic ventricular tachycardia (CPVT). The first-in-human (FIH) safety study will focus on obtaining safety data in adult participants. Cohort 1 and Cohort 2 (optional for dose exploration) will include participants ≥ 18 years of age. Cohort 3 will include participants ≥ 7 to < 18 years of age and will be initiated following data and safety monitoring board (DSMB) recommendations. Participants will be monitored for 5 years post-administration of SGT-501 including the active treatment period (1 year) and long-term follow-up (LTFU) (4 years) period.

Inclusion Criteria:

Type of Participant and Disease Characteristics:

• Clinical diagnosis of CPVT, based on documented history of polymorphic or bidirectional non-sustained ventricular tachycardia with exercise or ventricular ectopy in a pattern consistent with CPVT on EST.
• Central Screening laboratory determination of a RYR2 variant that is pathogenic or likely pathogenic for CPVT.
• Documented history of life-threatening ventricular arrhythmic event defined as: survived sudden cardiac arrest, sudden cardiac arrest with appropriate implantable cardioverter defibrillator (ICD) shock, arrhythmic syncope, or sustained ventricular tachycardia (30 seconds or more) with or without ICD shock.
• On stable dose (defined as no change in dose by more than 50% for at least 1 month prior to Screening) of standard-of-care therapy defined as a beta-blocker and/or flecainide.
• Documented prior history of EST demonstrating a ventricular arrythmia score (VAS) score of ≥ 2.
• For the first 2 participants in each cohort only: a properly functioning ICD device in place. Following review of data from Cohorts 1 and 2, the Data Safety and Monitoring Board (DSMB) will determine if this criterion is required for participants in Cohort 3.
• Must be up to date with meningococcal vaccination per national guidelines or willing to receive meningococcal vaccine to achieve this.
• Other inclusion criteria to be applied as per protocol.

Exclusion Criteria:

• Abnormal liver function: gamma-glutamyl transferase (GGT) > 1.5 × upper limit of normal [ULN] or total bilirubin > ULN).
• Abnormal renal function defined by estimated glomerular filtration rate < 60 milliliter /minute (mL/min)/1.73-square meter (m^2) using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Formula.
• Clinically significant abnormalities of coagulation including international normalized ratio or activated partial thromboplastin time > 1.2 × ULN or platelets < 150,000 cells/cubic millimeter (mm^3).
• Potential concomitant cardiomyopathy or inherited arrhythmia as evidenced by pathogenic or likely pathogenic mutation other than RYR2 obtained on cardiac panel during Screening.
• Current or prior treatment with an approved or investigational gene transfer drug.
• Exposure to another investigational drug within 90 days prior to Screening or 5 half-lives since last administration, whichever is longer.
• Contraindication or unwillingness to receive required immunosuppression regimen.
• Body mass index ≥ 30 kilograms per square meter (kg/m^2).
• Other exclusion criteria to be applied as per protocol.