Thomas J W, Kuo M D, Chawla M, Waugh J M, Yuksel E, Wright K C, Gerrity P M, Shenaq S M, Whigham C J, Fisher R G
Division of Diagnostic Imaging, Vascular and Interventional Section, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Radiographics. 1998 Nov-Dec;18(6):1373-94. doi: 10.1148/radiographics.18.6.9821188.
Gene therapy is an exciting frontier in medicine today. Radiologists will be involved in tracking the effects of these new therapies through imaging. Vascular and interventional radiology techniques also are ideally suited for minimally invasive, readily monitored gene delivery. Gene therapy is accomplished through gene augmentation or gene blocking. The latter is accomplished through antisense oligonucleotides or transcription factor decoys. Vectors are agents that facilitate gene delivery and expression and can be viral or nonviral. The vascular wall is an ideal target for gene therapy because of its central role in many biologic processes and its ready accessibility. Recombinant genes can be delivered ex vivo and in vivo, with the latter approaches involving open surgical, percutaneous injection, and endovascular catheter-based methods. Perforated, hydrogel-coated, and double balloon catheters have been used with varying success. Optimal catheter systems for gene transfer will enable delivery of the vector to the precise anatomic location with transfection limited to the cells of interest and will minimize shedding of the vector to distal sites, systemic effects of the therapeutic agent, and morbidity from the delivery method. Radiologists must become familiar with the basic rationale, strategies, and mechanisms of gene therapy and involved in its clinical trials to ensure an active role in this field.
基因治疗是当今医学中一个令人兴奋的前沿领域。放射科医生将通过成像参与追踪这些新疗法的效果。血管和介入放射学技术也非常适合微创、易于监测的基因递送。基因治疗是通过基因增强或基因阻断来实现的。后者是通过反义寡核苷酸或转录因子诱饵来完成的。载体是促进基因递送和表达的媒介,可以是病毒载体或非病毒载体。血管壁是基因治疗的理想靶点,因为它在许多生物过程中起着核心作用且易于接近。重组基因可以在体外和体内递送,后者包括开放手术、经皮注射和基于血管内导管的方法。穿孔导管、水凝胶涂层导管和双球囊导管已被使用,但效果各异。用于基因转移的最佳导管系统将能够将载体递送到精确的解剖位置,使转染仅限于感兴趣的细胞,并将载体向远端部位的脱落、治疗剂的全身效应以及递送方法的发病率降至最低。放射科医生必须熟悉基因治疗的基本原理、策略和机制,并参与其临床试验,以确保在该领域发挥积极作用。