Gene therapy for diabetic retinopathy

Table 1 Ongoing and recent gene therapy programs relevant to diabetic retinopathy and diabetic macular edema (as described in the manuscript)

Ref.	Program (vector)	Target indication/population	Delivery route	Vector/construct	Intended mechanism (as stated)	Trial phase/record in manuscript	Key points reported in the manuscript
Odio-Herrera et al[19], 2025	ABBV-RGX-314 (RGX-314)	Diabetic retinopathy with and without center-involved DME; studies described as enrolling moderately severe or severe NPDR (and select mild PDR) with good baseline vision and no recent anti-VEGF exposure	Suprachoroidal (single administration)	Described as AAV8-RGX-314 (ABBV-RGX-314); encodes an anti-VEGF-A Fab (ranibizumab-like) in the broader discussion	Durable intraocular anti-VEGF activity via a “retinal biofactory” strategy	Phase 2 ALTITUDE; ClinicalTrials.gov NCT04567550[37]	Development framed as testing whether durable anti-VEGF expression can be achieved in the diabetic retinal milieu; preliminary updates described as suggesting DRSS improvement and treatment-burden reduction in programs including ALTITUDE
Odio-Herrera et al[19], 2025	Ixoberogene soroparvovec (ADVM-022; ixo-vec)	DME	Intravitreal (single administration)	Described as AAV.7m8-aflibercept (AAV2.7m8 capsid driving aflibercept expression)	Sustained intraocular aflibercept exposure (“biofactory”) to reduce the need for repeated injections	Phase 2 INFINITY; ClinicalTrials.gov NCT04418427[38]	Manuscript highlights the counterbalancing safety risk in DME: Severe intraocular inflammation and hypotony (dose-dependent), prompting discontinuation of development for DME; ClinicalTrials.gov record described as 36 participants, unmasked April 2021 for enhanced safety monitoring after SUSAR in the high-dose arm; inflammation often mild–moderate and responsive to steroid drops, but dose-limiting toxicities impacted benefit–risk
Odio-Herrera et al[19], 2025	4D-150	Adults with DME	Intravitreal	Engineered to express aflibercept and also inhibit VEGF-C (via a VEGF-C - inhibitory microRNA); described as a multi-target intravitreal platform	Sustained anti-angiogenic activity with broader pathway coverage (VEGF-A + VEGF-C modulation)	Phase 2 SPECTRA; ClinicalTrials.gov NCT05930561[39]	Manuscript states the translational pivot is being tested directly in diabetic retinal disease via SPECTRA (4D-150 vs aflibercept); preliminary updates described as suggesting DRSS improvement and treatment-burden reduction in programs including SPECTRA

DR: Diabetic retinopathy; DME: Diabetic macular edema; NPDR: Non-proliferative diabetic retinopathy; PDR: Proliferative diabetic retinopathy; DRSS: Diabetic retinopathy severity score; VEGF: Vascular endothelial growth factor; AAV: Adeno-Associated Virus; SUSAR: Suspected unexpected serious adverse reaction.