Snyder Richard O, Francis Joyce
Powell Gene Therapy Center, Department of Molecular Genetics and Microbiology, University of Florida, College of Medicine, PO Box 100266, 1600 SW Archer Road, Gainesville, FL 32610-0266, USA.
Curr Gene Ther. 2005 Jun;5(3):311-21. doi: 10.2174/1566523054065066.
Recombinant adeno-associated viral (rAAV) vectors can mediate the safe and long-term correction of genetic diseases in animal models following a single administration. These pre-clinical studies are the basis of human trials that have shown rAAV vector persistence and safety in humans following delivery to lung, sinus, skeletal muscle, brain and liver. Transient disease correction has also been demonstrated in humans treated for hemophilia B and cystic fibrosis using AAV2 vectors. The physiochemical properties of rAAV vector virions are amenable to industry accepted manufacturing methodologies, long-term storage and direct in vivo administration. Recombinant adeno-associated virus vectors are manufactured in compliance with current Good Manufacturing Practices (cGMPs) as outlined in the Code of Federal Regulations (21CFR). To meet these requirements, manufacturing controls and quality systems are established, including 1) adequate facilities and equipment, 2) personnel who have relevant education or experience and are trained for specific assigned duties, 3) raw materials that are qualified for use and 4) a process (including production, purification, formulation, filling, storage and shipping) that is controlled, aseptic, reliable and consistent. Quality systems including Quality Control (QC) and Quality Assurance (QA) are also implemented. These manufacturing procedures and quality systems are designed so the product meets its release specifications to ensure that patients receive a safe, pure, potent and stable investigational drug.
重组腺相关病毒（rAAV）载体单次给药后可在动物模型中介导遗传性疾病的安全长期矫正。这些临床前研究是人体试验的基础，人体试验已表明rAAV载体在递送至肺、鼻窦、骨骼肌、脑和肝脏后在人体中的持久性和安全性。使用AAV2载体治疗血友病B和囊性纤维化的患者也已证明疾病得到了短暂矫正。rAAV载体病毒粒子的物理化学性质适用于业界公认的生产方法、长期储存和直接体内给药。重组腺相关病毒载体按照《联邦法规》（21CFR）中概述的现行良好生产规范（cGMP）进行生产。为满足这些要求，建立了生产控制和质量体系，包括1）足够的设施和设备，2）具有相关教育或经验并经过特定职责培训的人员，3）合格的原材料，以及4）一个受控、无菌、可靠且一致的过程（包括生产、纯化、制剂、灌装、储存和运输）。还实施了包括质量控制（QC）和质量保证（QA）在内的质量体系。设计这些生产程序和质量体系，以便产品符合其放行标准，确保患者接受安全、纯净、有效且稳定的研究药物。
