Siontas Oliver, Ahn Seungkuk
Eidgenössische Technische Hochschule (ETH) Zürich, Department of Biosystems Science and Engineering, 4056 Basel, Switzerland.
UCD Charles Institute of Dermatology, School of Medicine, University College Dublin, D04 V1W8 Dublin, Ireland.
J Clin Med. 2024 Dec 4;13(23):7385. doi: 10.3390/jcm13237385.
Retinal diseases, leading to various visual impairments and blindness, are on the rise. However, the advancement of retinal gene therapies offers new hope for treatment of such diseases. Among different vector systems for conferring therapeutic genetic load to retinal cells, adeno-associated viruses (AAVs) have been most intensively explored and have already successfully gained multiple clinical approvals. AAV-based retinal gene therapies have shown great promise in treating retinal disorders, but usually rely on the heavily disruptive administration methods such as subretinal injection. This is because the clinically well-established, minimally invasive alternative of intravitreal injection (IVI) necessitates AAVs to traverse the retinal inner limiting membrane (ILM), which is hard to penetrate in higher eye models, like human or porcine eyes. Additionally, AAVs' natural transduction preference, known as tropism, is commonly not specific to cells of only one target retinal layer, which is another ongoing challenge in retinal gene therapy. This review examines strategies to overcome these obstacles with a focus on the potential of magnetic nanoparticles (MNPs) for improved retinal AAV delivery.
导致各种视力障碍和失明的视网膜疾病正在增加。然而，视网膜基因治疗的进展为治疗此类疾病带来了新的希望。在将治疗性基因载荷传递给视网膜细胞的不同载体系统中，腺相关病毒（AAV）得到了最深入的研究，并且已经成功获得了多项临床批准。基于AAV的视网膜基因治疗在治疗视网膜疾病方面显示出巨大的潜力，但通常依赖于如视网膜下注射等具有高度破坏性的给药方法。这是因为临床上成熟的、微创的玻璃体腔内注射（IVI）替代方法要求AAV穿过视网膜内界膜（ILM），而在如人眼或猪眼等高等级眼部模型中，这层膜很难穿透。此外，AAV的自然转导偏好，即所谓的嗜性，通常并非仅对一个目标视网膜层的细胞具有特异性，这是视网膜基因治疗中另一个持续存在的挑战。本综述探讨了克服这些障碍的策略，重点关注磁性纳米颗粒（MNP）改善视网膜AAV递送的潜力。
