Inclusion Criteria:

• Participant is capable of providing signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol
• Must be 18 to 75 years of age (inclusive) at Screening
• Body Mass Index (BMI) of 25 to <40 kg/m2 (inclusive)
• Male participants must agree to use a highly effective contraception during the Treatment Period and at least 12 months after administration of VV-14303. Female participants must not be a woman of child-bearing potential (WOCBP)
• Biopsy-confirmed MASH
• Previous history or presence of ≥2 of the following metabolic risk factors: obesity (BMI ≥25 kg/m²), hypertension (blood pressure [BP] ≥140/90 mmHg or on antihypertensive medication), dyslipidemia (triglycerides ≥150 mg/dL or high-density lipoprotein cholesterol [HDL-C] <40 mg/dL in men/<50 mg/dL in women or on lipid-lowering therapy), type 2 diabetes mellitus
• Must be willing to refrain from the donation of blood, plasma, platelets, eggs, or sperm during the 12-month post-treatment follow-up period

Exclusion Criteria:

• Presence of alternate and/or additional liver disease etiologies at Screening, including but not limited to chronic viral hepatitis, autoimmune hepatitis

• Use of treatments for metabolic syndrome management, including oral antidiabetic drugs (OADs) (e.g., metformin), incretin mimetics (GLP-1 receptor agonists or GLP-1/gastric inhibitory polypeptide [GIP] agonists) or other glucose-lowering agents that has not been stable for at least 6 months prior to Screening

• Use of Resmetirom that has not been stable for at least 6 months prior to Screening visit

• Any medical, cognitive, or psychiatric condition that, in the opinion of the Investigator, could contraindicate the use of the investigational drug, make consistent study assessment and follow-up over the 12-month Post-Treatment Follow-up Period unlikely, or would make the participant an unsafe study candidate.

• Type 1 diabetes, or poorly controlled type 2 diabetes (HbA1c > 8.0% at Screening)

• History of major trauma to the muscle(s) intended for IM injection meeting any of the following criteria:

  1. Within 6 months prior to Screening, or
  2. At any timepoint prior to Screening with continued neurologic or musculoskeletal symptoms

• Prior participation in any systemic experimental treatment or receiving any other systemic investigational treatment including within 6 weeks or 5 half-lives of the active ingredient (whichever is longer) prior to the start of Screening

• Any vaccination or planned vaccination 30 days prior to dosing, or planned vaccination 8 weeks post dosing

• Previously received AAV or adenoviral therapy or participation in any previous gene therapy trial