Neutrally charged phosphorodiamidate morpholino antisense oligomers: Uptake, efficacy and pharmacokinetics

被引:49
作者
Arora, V [1 ]
Devi, GR [1 ]
Iversen, PL [1 ]
机构
[1] AVI BioPharma Inc, Res & Dev, Corvallis, OR 97333 USA
关键词
cancer; genomics; c-myc; prostate; phosphorothioate; delivery; fluorescence; PMO;
D O I
10.2174/1389201043376706
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Antisense technology constitutes development of sequence-specific DNA or RNA analogs that can block the activity of selected single-stranded genetic sequences and offer the potential of high specificity lacking in many current drug treatments. The sequencing of the human genome has greatly increased the potential of this approach. Antisense oligonucleotides, the most commonly used antisense approach, are unmodified or chemically modified single stranded RNA or DNA molecules specifically designed to hybridize to corresponding RNA by Watson-Crick binding. Phosphorodiamidate Morpholino oligomers (PMO) are a novel class of non-ionic antisense agents that inhibit gene expression by binding to RNA and sterically blocking processing or translation. PMOs have shown excellent efficiency and safety profile via various routes of administration in multiple animal and human studies. This review will summarize the preclinical studies with PMOs on the road to their development as therapeutic agents with particular emphasis on in vivo biodistribution and pharmacokinetics.
引用
收藏
页码:431 / 439
页数:9
相关论文
共 83 条
[71]   Morpholino antisense oligomers: Design, preparation, and properties [J].
Summerton, J ;
Weller, D .
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT, 1997, 7 (03) :187-195
[72]   Morpholino antisense oligomers: the case for an RNase H-independent structural type [J].
Summerton, J .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 1999, 1489 (01) :141-158
[73]   Antisense properties of morpholino oligomers [J].
Summerton, J ;
Weller, D .
NUCLEOSIDES & NUCLEOTIDES, 1997, 16 (7-9) :889-898
[74]   Morpholino and phosphorothioate antisense oligomers compared in cell-free and in-cell systems [J].
Summerton, J ;
Stein, D ;
Huang, SB ;
Matthews, P ;
Weller, D ;
Partridge, M .
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT, 1997, 7 (02) :63-70
[75]   Restoration of human β-globin gene expression in murine and human IVS2-654 thalassemic erythroid cells by free uptake of antisense oligonucleotides [J].
Suwanmanee, T ;
Sierakowska, H ;
Lacerra, G ;
Svasti, S ;
Kirby, S ;
Walsh, CE ;
Fucharoen, S ;
Kole, R .
MOLECULAR PHARMACOLOGY, 2002, 62 (03) :545-553
[76]  
Tari A M, 2001, Curr Opin Investig Drugs, V2, P1450
[77]   Effect of TNF-α antisense oligomers on cytokine production by primary murine alveolar macrophages [J].
Taylor, MF ;
Weller, DD ;
Kobzik, L .
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT, 1998, 8 (03) :199-205
[78]  
Thierry AR, 2003, CURR OPIN MOL THER, V5, P133
[79]  
Wallace TL, 1998, APPLIED ANTISENSE OLIGONUCLEOTIDE TECHNOLOGY, P407
[80]   DIRECT GENE-TRANSFER INTO MOUSE MUSCLE INVIVO [J].
WOLFF, JA ;
MALONE, RW ;
WILLIAMS, P ;
CHONG, W ;
ACSADI, G ;
JANI, A ;
FELGNER, PL .
SCIENCE, 1990, 247 (4949) :1465-1468