Wasala Lakmini P, Hakim Chady H, Yue Yongping, Yang N Nora, Duan Dongsheng
Department of Veterinary Pathobiology, College of Veterinary Medicine, The University of Missouri, Columbia, MO, USA.
Department of Molecular Microbiology and Immunology, School of Medicine, The University of Missouri, Columbia, MO, USA.
Methods Mol Biol. 2019;1937:281-294. doi: 10.1007/978-1-4939-9065-8_18.
Many diseases affect multiple tissues and/or organ systems, or affect tissues that are broadly distributed. For these diseases, an effective gene therapy will require systemic delivery of the therapeutic vector to all affected locations. Adeno-associated virus (AAV) has been used as a gene therapy vector for decades in preclinical studies and human trials. These studies have shown outstanding safety and efficacy of the AAV vector for gene therapy. Recent studies have revealed yet another unique feature of the AAV vector. Specifically, AAV can lead to bodywide gene transfer following a single intravascular injection. Here we describe the protocols for effective systemic delivery of AAV in both neonatal and adult mice and dogs. We also share lessons we learned from systemic gene therapy in the murine and canine models of Duchenne muscular dystrophy.
许多疾病会影响多个组织和/或器官系统,或者影响广泛分布的组织。对于这些疾病,有效的基因治疗将需要将治疗载体全身性递送至所有受影响的部位。几十年来,腺相关病毒(AAV)已在临床前研究和人体试验中用作基因治疗载体。这些研究表明,AAV载体用于基因治疗具有出色的安全性和有效性。最近的研究揭示了AAV载体的另一个独特特征。具体而言,单次血管内注射后,AAV可导致全身基因转移。在这里,我们描述了在新生小鼠和成年小鼠及犬中有效全身性递送AAV的方案。我们还分享了我们在杜兴氏肌营养不良症的小鼠和犬模型中进行全身基因治疗所学到的经验教训。