Design and applications of modified oligonucleotides

被引:24
作者
Gallo, M
Montserrat, JM
Iribarren, AM
机构
[1] Univ Buenos Aires, CONICET, Inst Invest Ingn Genet & Biol Mol, Lab Quim Acidos Nucleicos, RA-1428 Buenos Aires, DF, Argentina
[2] Univ Nacl Gen Sarmiento, Inst Ciencias, Buenos Aires, DF, Argentina
[3] Univ Nacl Quilmes, Ctr Estudios & Invest, Buenos Aires, DF, Argentina
关键词
modified nucleotides; antisense; ribozymes; oligonucleotide libraries; aptamers; SELEX method;
D O I
10.1590/S0100-879X2003000200001
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Oligonucleotides have a wide range of applications in fields such as biotechnology, molecular biology, diagnosis and therapy. However, the spectrum of uses can be broadened by introducing chemical modifications into their structures. The most prolific field in the search for new oligonucleotide analogs is the antisense strategy, where chemical modifications confer appropriate characteristics such as hybridization, resistance to nucleases, cellular uptake, selectivity and, basically, good pharmacokinetic and pharmacodynamic properties. Combinatorial technology is another research area where oligonucleotides and their analogs are extensively employed. Aptamers, new catalytic ribozymes and deoxyribozymes are RNA or DNA molecules individualized from a randomly synthesized library on the basis of a particular property. They are identified by repeated cycles of selection and amplification, using PCR technologies. Modified nucleotides can be introduced either during the amplification procedure or after selection.
引用
收藏
页码:143 / 151
页数:9
相关论文
共 36 条
[1]   Importance of nucleotide sequence and chemical modifications of antisense oligonucleotides [J].
Agrawal, S .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 1999, 1489 (01) :53-68
[2]   Second-generation antisense oligonucleotides: Structure-activity relationships and the design of improved signal-transduction inhibitors [J].
Altmann, KH ;
Fabbro, D ;
Dean, NM ;
Geiger, T ;
Monia, BP ;
Muller, M ;
Nicklin, P .
BIOCHEMICAL SOCIETY TRANSACTIONS, 1996, 24 (03) :630-637
[3]   SELECTION OF SINGLE-STRANDED-DNA MOLECULES THAT BIND AND INHIBIT HUMAN THROMBIN [J].
BOCK, LC ;
GRIFFIN, LC ;
LATHAM, JA ;
VERMAAS, EH ;
TOOLE, JJ .
NATURE, 1992, 355 (6360) :564-566
[4]   Designing ribozymes for the inhibition of gene expression [J].
Bramlage, B ;
Luzi, E ;
Eckstein, F .
TRENDS IN BIOTECHNOLOGY, 1998, 16 (10) :434-438
[5]   Molecular biology - Making catalytic DNAs [J].
Breaker, RR .
SCIENCE, 2000, 290 (5499) :2095-2096
[6]   ENCODED COMBINATORIAL CHEMISTRY [J].
BRENNER, S ;
LERNER, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (12) :5381-5383
[7]  
Cech T. R., 1993, RNA WORLD
[8]   AN UNNATURAL BIOPOLYMER [J].
CHO, CY ;
MORAN, EJ ;
CHERRY, SR ;
STEPHANS, JC ;
FODOR, SPA ;
ADAMS, CL ;
SUNDARAM, A ;
JACOBS, JW ;
SCHULTZ, PG .
SCIENCE, 1993, 261 (5126) :1303-1305
[9]   Synthesis and properties of (2′S)- and (2′R)-2′-deoxy-2′-C-methyl oligonucleotides [J].
Cicero, DO ;
Gallo, M ;
Neuner, PJ ;
Iribarren, AM .
TETRAHEDRON, 2001, 57 (36) :7613-7621
[10]   Comprehensive survey of combinatorial library synthesis: 1998 [J].
Dolle, RE ;
Nelson, KH .
JOURNAL OF COMBINATORIAL CHEMISTRY, 1999, 1 (04) :235-282