Valdmanis Paul N, Kay Mark A
Departments of Pediatrics and Genetics, Stanford University , Stanford, California.
Hum Gene Ther. 2017 Apr;28(4):361-372. doi: 10.1089/hum.2016.171. Epub 2017 Jan 10.
The use of recombinant adeno-associated viruses (rAAVs) ushered in a new millennium of gene transfer for therapeutic treatment of a number of conditions, including congenital blindness, hemophilia, and spinal muscular atrophy. rAAV vectors have remarkable staying power from a therapeutic standpoint, withstanding several ebbs and flows. As new technologies such as clustered regularly interspaced short palindromic repeat genome editing emerge, it is now the delivery tool-the AAV vector-that is the stalwart. The long-standing safety of this vector in a multitude of clinical settings makes rAAV a selling point in the advancement of approaches for gene replacement, gene knockdown, gene editing, and genome modification/engineering. The research community is building on these advances to develop more tailored delivery approaches and to tweak the genome in new and unique ways. Intertwining these approaches with newly engineered rAAV vectors is greatly expanding the available tools to manipulate gene expression with a therapeutic intent.
重组腺相关病毒(rAAV)的使用开启了基因转移的新纪元,用于治疗多种疾病,包括先天性失明、血友病和脊髓性肌萎缩症。从治疗角度来看,rAAV载体具有显著的持久性,历经多次起伏。随着诸如成簇规律间隔短回文重复序列基因组编辑等新技术的出现,如今作为递送工具的AAV载体成为了中流砥柱。该载体在众多临床环境中长期保持安全,这使得rAAV成为基因替代、基因敲低、基因编辑和基因组修饰/工程方法发展中的一个卖点。研究界正在基于这些进展开发更具针对性的递送方法,并以新颖独特的方式调整基因组。将这些方法与新工程化的rAAV载体相结合,极大地扩展了用于治疗目的操纵基因表达的可用工具。