Stone Laura S, Vulchanova Lucy
Department of Neuroscience, University of Minnesota, 6-125 Jackson Hall, 321 Church Street S.E., Minneapolis, MN 55455, USA.
Adv Drug Deliv Rev. 2003 Aug 28;55(8):1081-112. doi: 10.1016/s0169-409x(03)00105-4.
As the genomic revolution continues to evolve, there is an increasing demand for efficient and reliable tools for functional characterization of individual gene products. Antisense oligonucleotide-mediated knockdown has been used successfully as a functional genomics tool in animal models of pain and analgesia yet skepticism regarding the validity and utility of antisense technology remains. Contributing to this uncertainty are the lack of systematic studies exploring antisense oligonucleotide use in vivo and the many technical and methodological challenges intrinsic to the method. This article reviews the contributions of antisense oligonucleotide-based studies to the field of pain and analgesia and the general principles of antisense technology. A special emphasis is placed on technical issues surrounding the successful application of antisense oligonucleotides in vivo, including sequence selection, antisense oligonucleotide chemistry, DNA controls, route of administration, uptake, dose-dependence, time-course and adequate evaluation of knockdown.
随着基因组革命的不断发展，对用于单个基因产物功能表征的高效可靠工具的需求日益增加。反义寡核苷酸介导的基因敲低已成功用作疼痛和镇痛动物模型中的功能基因组学工具，但对反义技术的有效性和实用性仍存在怀疑。导致这种不确定性的原因包括缺乏探索反义寡核苷酸体内应用的系统研究，以及该方法固有的许多技术和方法挑战。本文综述了基于反义寡核苷酸的研究对疼痛和镇痛领域的贡献以及反义技术的一般原则。特别强调了围绕反义寡核苷酸在体内成功应用的技术问题，包括序列选择、反义寡核苷酸化学、DNA对照、给药途径、摄取、剂量依赖性、时间进程以及基因敲低的充分评估。
