A surgically compatible shape memory alloy electroporation electrode for delivering DNA to the living retina

The successful application of adeno-associated virus (AAV)-mediated DNA delivery has opened a new era in the gene therapy of retinal diseases. Electroporation (EP) has the potential to avoid the drawbacks of AAV-mediated delivery, such as limited cargo size and unresolved safety concerns. Unfortunately, all reported EP devices are not compatible with standard ocular surgical procedures, preventing the clinical exploration of EP-mediated delivery of therapeutic DNA. To address this issue, a surgically compatible EP device has been developed for localized in vivo retinal gene delivery. The key component is a shape memory alloy (SMA) based Self-Coiling Spiral Intraocular Electrode (Secospine). Before surgical employment, the electrode is a thin wire with a diameter of 0.15 mm, which can be easily inserted into the eyeball through a standard trocar device. Once placed inside the eyeball, the electrode recovers into a disc shape upon temperature activation and produces an appropriate electrical field in a specific region of the retina. Hence, previously injected DNA can be transfected into the living retina with minimal tissue damage. By optimizing the electrode profile and applied voltage, satisfactory transfection efficiency has been achieved in both ex vivo and in vivo assays of rabbit retina at 20 V. This study provides a promising tool for the clinical delivery of DNA into the living retina by standard minimally invasive surgery, bridging the gap between the laboratory demonstration and clinical application of retinal EP.