Summary of the plasmid based gene therapies to promote diabetic foot ulcer (DFU) healing.
| Study | Aim of the study/phase | Subjects/intervention | Outcome |
|---|---|---|---|
| Perin et al. [89] | A phase 3, double-blind, randomised, placebo-controlled, multicenter 7-month study for the efficacy and safety of VM202. | 44 patients with DFU.VM202 was injected via 16 injections (4 mg total per visit) into the ipsilateral calf of the affected foot on days 0, 14, 28, and 42. | 23 patients with neuroischemic ulcers: significantly increased complete ulcer closure at months 3, 4, and 5 (P = 0.0391, 0.0391, and 0.0361).Increase in ABI in the treatment group.Phase 3 was discontinued due to slow patient recruitment, mixed efficacy results in earlier studies, and a need for further validation to prove it outperforms existing standard care. |
| Barć et al. [85] | A clinical study to evaluate the safety and efficacy.A phase of therapeutic trial. | 12 patients with gene therapy (treatment group).12 patients without gene therapy.First injection of pIRES/VEGF165/HGF followed by ANG1 plasmid injection after one month in treatment group. | Significantly improved healing in the treatment group associated with increased ABI, PtcO2 and decreased resting pain.Not in clinics yet because of high manufacturing costs, regulatory complexities, safety concerns regarding gene delivery, and the need for more robust, large-scale clinical trial data. |
| Chung et al. [96] | In-vitro study to evaluate the effects of EGF. | Multiple cell linesMultiple human EGF isoforms were transfected. | EGF828 including a membrane-anchoring domain was released as mature EGF protein.EGF plasmid may be effective as non-viral gene therapy.Not in clinics due to the lack of approved, large-scale clinical trials proving safety and efficacy, high development costs, and the technical challenges of delivering nucleic acids to chronic wounds. |
| Ko et al. [97] | In-vivo study to compare EGF and VEGF effects on wound healing in diabetic C57BL/6J mice. | FRM-EGF828 or minicircle VEGF165 were prepared using p2øC31 plasmid and a mixture of minicircle-VEGF165 (20 µg) and pβ-EGF828 (20 µg) with microbubble solution (100 µg) was injected subcutaneously. | Accelerated wound therapy with gene therapy.VEGF was better than EGF for angiogenesis and increased blood circulation.Wound healing rates and histological findings were more accelerated in the EGF gene therapy compared to VEGF.Not in clinics due lack of lack of approved, large-scale clinical trials proving safety and efficacy. |
ABI: ankle-brachial index; ANG1: angiopoietin 1; HGF: hepatocyte growth factor; PtcO2: transcutaneous oxygen pressure measurement; VEGF: vascular endothelial growth factor.
IFA: Writing—original draft. VAG: Writing—original draft. VR: Conceptualization, Writing—original draft, Writing—review & editing. All authors read and approved the submitted version.
The authors declare that they have no conflicts of interest.
Insert content.
Not applicable.
Not applicable.
Not applicable.
The authors received no specific funding for this study.
© The Author(s) 2026.
Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.