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
