antisense oligonucleotides;
RNA interference;
siRNA;
clinical trials;
cancer therapeutics;
D O I:
10.1615/CritRevEukaryotGeneExpr.v15.i2.50
中图分类号:
Q81 [生物工程学(生物技术)];
Q93 [微生物学];
学科分类号:
071005 ;
0836 ;
090102 ;
100705 ;
摘要:
Most cancers are characterized by abnormal gene expression, which is thought to contribute to the pathogenesis and maintenance of the malignant phenotype; abnormal proliferation, maturation, and apoptosis. Silencing such genes would appear to be a rational approach to the therapy of cancer, and some preliminary clinical studies support this concept. Of the strategies available, the anti-mRNA gene silencing approach has attracted much attention and is the focus of this review. This strategy includes three types of agents: (1) single-stranded antisense ohgonudeotides; (2) catalytically active oligonucleotides, such as ribozymes, and DNAzymes that possess inherent RNA cleaving activity, and (3) small interfering RNA (siRNA) molecules that induce RNA interference (RNAi). Among these agents, antisense ohgonudeotides, especially phosphorothioate (PS) oligonucleotides, have been the most frequently used in clinical trials. In this article, we provide an overview of anti-mRNA gene silencing agents and their development for use as cancer therapeutics.
机构:
Brown Univ, Warren Alpert Med Sch, Dept Pathol & Lab Med, Providence, RI 02912 USA
Brown Univ, Legorreta Canc Ctr, Providence, RI 02912 USABrown Univ, Warren Alpert Med Sch, Dept Pathol & Lab Med, Providence, RI 02912 USA
机构:
Fred Hutchinson Canc Res Ctr, Div Basic Sci, 1100 Fairview Ave N, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Div Basic Sci, 1100 Fairview Ave N, Seattle, WA 98109 USA
Stoddard, Barry L.
Khvorova, Anastasia
论文数: 0引用数: 0
h-index: 0
机构:
Univ Massachusetts, Med Sch, RNA Therapeut Inst, 368 Plantat St, Worcester, MA 01605 USAFred Hutchinson Canc Res Ctr, Div Basic Sci, 1100 Fairview Ave N, Seattle, WA 98109 USA
Khvorova, Anastasia
Corey, David R.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Texas Southwestern Med Ctr Dallas, Dept Pharmacol, 6001 Forest Pk Rd, Dallas, TX 75390 USA
Univ Texas Southwestern Med Ctr Dallas, Dept Biochem, 6001 Forest Pk Rd, Dallas, TX 75390 USAFred Hutchinson Canc Res Ctr, Div Basic Sci, 1100 Fairview Ave N, Seattle, WA 98109 USA
Corey, David R.
Dynan, William S.
论文数: 0引用数: 0
h-index: 0
机构:
Emory Univ, Sch Med, Rollins Res Ctr 4127, Dept Biochem, 1510 Clifton Rd NE, Atlanta, GA 30322 USA
Emory Univ, Sch Med, Rollins Res Ctr 4127, Dept Radiat Oncol, 1510 Clifton Rd NE, Atlanta, GA 30322 USAFred Hutchinson Canc Res Ctr, Div Basic Sci, 1100 Fairview Ave N, Seattle, WA 98109 USA
Dynan, William S.
Fox, Keith R.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Southampton, Ctr Biol Sci, Life Sci Bldg 85, Southampton SO17 1BJ, Hants, EnglandFred Hutchinson Canc Res Ctr, Div Basic Sci, 1100 Fairview Ave N, Seattle, WA 98109 USA