Key Inclusion Criteria (Part A):
1. Willing and able to provide written informed consent form
2. Be aged 18 to 45 years (inclusive) at the time of signing the informed consent form
3. Generally healthy on medical history, exam, labs, and ECG
4. BCVA 20/25 or better in each eye
5. Serum retinol above protocol threshold
6. Body weight ≥40 kg and BMI of 18.0 to 32.0 kg/m2
7. Men and WOCBP must agree to use highly effective methods of contraception or practice abstinence from 30 days before the first dose of CITY-RBP4, throughout the study, and for at least 180 days after treatment with CITY-RBP4 or the last study visit, whichever is longer; men must refrain from donating or banking sperm during the same period
8. Female participants who are not WOCBP should meet at least 1 of the following criteria: have undergone a documented hysterectomy, bilateral oophorectomy, and/or bilateral salpingectomy; have medically confirmed ovarian failure, or achieved postmenopausal status
Key Exclusion Criteria (Part A):
1. Clinically significant ocular disease or prior ocular surgery that could interfere with safety assessments
2. History of vitamin A deficiency, malabsorption, or chronic diarrhea
3. Clinically significant cardiac, hepatic, renal, pulmonary, neurologic, or psychiatric disease
4. Positive hepatitis B, hepatitis C, or HIV screening
5. Prior RNAi/oligonucleotide therapy or recent investigational treatment
6. Recent vitamin A-related supplements, retinoids, or medications affecting vitamin A metabolism
7. Pregnancy or breastfeeding, if applicable
Key Inclusion Criteria (Parts B and C)
1. Participants aged 12 to 45 years
2. Clinical diagnosis of STGD1 with documented ABCA4 pathogenic/likely pathogenic variant
3. Minimum BCVA is required in the study eye
4. Subjects must have a defined aggregate atrophic lesion in 1 or both eyes
5. Body weight ≥40 kg
6. Able to complete key ophthalmic safety assessments and comply with study precautions
Key Exclusion Criteria (Parts B and C)
1. Ocular conditions that could confound retinal imaging or safety evaluation
2. Prior ocular gene therapy, stem cell therapy, or retinal implant
3. Vitamin A deficiency or recent prohibited vitamin A-related treatments
4. Recent interventional study participation
5. Clinically significant non-ophthalmic disease, abnormal screening labs/ECG, or positive hepatitis B, hepatitis C, or HIV screening
6. Pregnancy or breastfeeding, if applicable
