In Vivo Correction of Inborn Errors of Metabolism Affecting the Liver and Kidney Using Next‑Generation Viral Vectors with Molecular Imaging Follow‑Up
DOI:
https://doi.org/10.70577/asce.v5i3.995Keywords:
Gene therapy; inborn errors of metabolism; AAV vectors; gene editing; molecular imaging; hepatorenal disease.Abstract
Inborn errors of metabolism (IEM) with hepatorenal involvement constitute a group of severe monogenic diseases characterized by progressive liver and kidney dysfunction, with high morbidity and mortality in early childhood. In vivo gene therapy has emerged as a potential curative option, particularly through next‑generation viral vectors enabling efficient and durable gene transfer. Non‑invasive monitoring of therapeutic efficacy remains a challenge that molecular imaging can address. This review analyzes the current status of in vivo correction of IEM with hepatorenal involvement using next‑generation viral vectors (AAV, lentivirus, and gene editing systems) and molecular imaging techniques for non‑invasive therapy follow‑up. A narrative review of the literature published between 2020 and 2026 in PubMed, Scopus, and Web of Science was conducted, selecting preclinical studies and clinical trials on gene therapy for hepatorenal IEM and molecular imaging techniques applied to gene therapy follow‑up. AAV vectors have demonstrated efficacy in animal models of maple syrup urine disease (MSUD) using dual‑function AAV9 vectors (Wang et al., 2025), CPS1 deficiency using oversized AAV8 vectors (Lipshutz et al., 2025), methylmalonic acidemia using AAV8 in phase I/II clinical trials (NCATS, 2025), and Fabry disease using AAV5 with enzyme activity increases of 27‑ to 208‑fold above normal levels (uniQure, 2025). Gene editing systems based on CRISPR‑Cas9 delivered by single AAV vectors have shown permanent correction in models of hemophilia B, protein C deficiency, and ornithine transcarbamylase deficiency (Batjargal et al., 2025). Molecular imaging, using PET with reporter systems such as DTPA‑R for AAV9 vector tracking (Nature Biomedical Engineering, 2025) and in situ sequencing for spatial mapping of gene editing events (Nature Biomedical Engineering, 2026), enables visualization of metabolic correction and gene editing in vivo. In vivo gene therapy with next‑generation viral vectors represents a transformative strategy for hepatorenal IEM. The integration of molecular imaging as a non‑invasive follow‑up tool allows for efficacy assessment, early detection of complications, and treatment personalization. Challenges such as immunogenicity, liver toxicity, and the need for redosing strategies remain. Controlled clinical trials are required to consolidate these therapies into clinical practice.
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