- 作者: Xue-Song Wu De-Pei Liu Chih-Chuan Liang
- 作者服務機構: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PRC
- 中文摘要: --
- 英文摘要: A strategy called targeted gene repair was developed tofacilitate the process of gene therapy using a chimericRNA-DNA oligonucleotide. Experiments demonstratedthe feasibility of using the chimeric oligonucleotide tointroduce point conversion in genes in vitro and in vivo. However, barriers exist in the low and/or inconstant fre-quency of gene repair. To overcome this difficulty, threemain aspects should be considered. One is designing amore effective structure of the oligonucleotide. Trialshave included lengthening the homologous region, dis-placing the mismatch on the chimeric strand and invent-ing a novel thioate-modified single-stranded DNA, whichwas demonstrated to be more active than the primarychimera in cell-free extracts. The second aspect is opti-mizing the delivery system. Producing synthetic carriersfor efficient and specific transfection is demanding, espe-cially for treatment in vivo where targeting is difficult.The third and most important aspect lies in the elucida-tion of the mechanism of the strategy. Investigation ofthe mechanism of strand exchange between the oligonu-cleotide molecule and double-stranded DNA in pro-karyotes may greatly help to understand the mechanismof gene repair in eukaryotes. The development of thisstrategy holds great potential for the treatment of geneticdefects and other purposes.
- 中文關鍵字: --
- 英文關鍵字: chimera. RNA-DNA oligonucleotide. Gene therapy. Targeted gene repair