Molecular mechanisms in podocytopathies: finding suitable targets for a new era of glomerular gene therapy - PubMed
3 days ago
- #gene therapy
- #podocytopathies
- #glomerular disorders
- Podocytopathies are glomerular disorders caused by podocyte dysfunction, leading to proteinuria and glomerulosclerosis.
- Key podocyte components involved include slit-diaphragm proteins (nephrin, podocin), cytoskeletal regulators (ACTN4, TRPC6), and adhesion complexes (integrins, dystroglycan).
- Current therapies often fail to address genetic or molecular defects, especially in hereditary or refractory cases.
- Gene therapy offers a transformative approach using AAV vectors, CRISPR-based editing, and RNA modulation to correct mutations or restore pathways.
- Recent advances include improved podocyte targeting via capsid engineering, tissue-specific promoters, and better delivery strategies.
- Preclinical successes include AAV-mediated rescue of NPHS2-associated nephrotic syndrome and complement modulation in IgA nephropathy.
- Challenges remain, such as immune responses, vector biodistribution, and disease heterogeneity.
- Future directions include patient-derived organoid models and combinatorial therapies for precision medicine in podocytopathies.