Clinically, fracture nonunion often leads to pain and disability in patients. Fracture nonunion often requires additional surgery to restore skeletal muscle function, so the treatment of fracture nonunion has always been a difficult point in the field of orthopedics. In recent years, with the development of genetic engineering, the technology of using gene to treat fracture nonunion has been widely studied. A large number of experiments have confirmed that the target genes encoding growth factors related to fracture healing are introduced into target cells through different delivery methods in vivo or in vitro, thereby expressing specific growth factors can promote fracture healing, which provides a new way for treating fracture nonunion. This article will discuss the research status of different delivery methods of osteogenic genes, as well as their advantages and disadvantages, in order to provide a theoretical basis for targeted gene therapy for fracture nonunion.
Gene therapy is designed to introduce genetic material into the cells of a patient via virus to enhance, inhibit, edit or add a genetic sequence, results in a therapeutic or prophylactic effect. Gene therapy has brought positive influence and great potential for the treatment of retinal diseases including genetic retinal diseases and acquired retinal diseases. In addition to the constant optimization of gene vectors, the exploration of different drug delivery techniques has brought different therapeutic effects for gene therapy of retinal diseases. The main delivery methods include subretinal injection, intravitreal injection, suprachoroidal injection. Considering the transfection efficiency and safety of delivery methods, emerging sub-inner limiting membrane injection and noninvasive gene delivery are under investigation. The selection of gene delivery method is very important for the safety and effectiveness of gene therapy for retinal diseases. It is not only related to the development of equipment and technology, but also related to the modification of adeno-associated virus, the selection of promoter and the specific retinal cells that the target gene wants to be transfected. Therefore, the most appropriate method of gene delivery should be selected according to the final gene therapy agent and the specific transfected cells after taking all these factors into consideration.
ObjectiveTo observe the safety of 2-port non-vitrectomized subretinal injection (SRI) for the treatment of Bietti crystalline dystrophy (BCD). MethodsA exploratory clinical study. From February to May 2023, 6 BCD patients with 6 eyes who were confirmed by examination in Xiamen Eye Center of Xiamen University and were treated with SRI adeno-associated virus vector transgenic drugs were included in the study. Among them, 2 males had 2 eyes and 4 females had 4 eyes. Age were 34-60 years old. The study eye underwent adeno associated virus gene therapy via 2-port non-vitrectomized SRI. Two scleral ports were created using 25G vitrectomy trocar to place the light pipe and injection cannula. Anterior chamber paracentesis was performed to lower intraocular pressure. Under the silicone oil infusion mode of the vitrectomy machine, a 38G injection cannula penetrated the retina to reach the subretinal space. The injection speed was controlled by the foot pedal of the vitrectomy machine, and the drug was slowly injected into the subretinal space to create a subretinal bleb. if intra-ocular pressure assessed by finger palpation was high at the end of injection, drainage of the aqueous humor can be made by compressing the cornea incision until the intraocular pressure was normal. Patients were followed for 9-12 months and be examined using the same equipment and methods as before. ResultsRetinal pigment epithelium and choroidal atrophy were observed in all 6 eyes of 6 patients were graded as stage Ⅲ by the fundus examination revealing atrophy of retinal pigmented epithelium and choroid, with or without yellow-white crystals and/or complex lipid. The range were operation time 9-14 minutes. No vitreous prolapse, retinal hemorrhage, or retinal tear was observed during surgery. After 24 hours, optical coherence tomogrophy examination showed absorption of subretinal fluid and retinal reattachment. None of the six patients showed corneal keratic precipitates, anterior chamber cells, vitreous cells, inflammation, high intraocular pressure, or retinal tear within the 9-month follow-up. ConclusionSubretinal injection without vitrectomy using two ports is a safe and feasible alternative for adult gene therapy, and it shortens the surgical time.