Antisense & nucleic acid drug development最新文献_第9页

From bugs to drugs: therapeutic immunomodulation with oligodeoxynucleotides containing CpG sequences from bacterial DNA. 从细菌到药物:用含有细菌DNA CpG序列的寡脱氧核苷酸进行治疗性免疫调节。

Antisense & nucleic acid drug development Pub Date : 2001-06-01 DOI: 10.1089/108729001300338717

A. Krieg

引用次数: 65

High-purity preparation of a large DNA dumbbell. 高纯度的大DNA哑铃制备。

Antisense & nucleic acid drug development Pub Date : 2001-06-01 DOI: 10.1089/108729001300338672

H. Kuhn, M. Frank-Kamenetskii, V. Demidov

引用次数: 9

Best minimally modified antisense oligonucleotides according to cell nuclease activity. 根据细胞核酸酶活性，最佳的最小修饰反义寡核苷酸。

Antisense & nucleic acid drug development Pub Date : 2001-06-01 DOI: 10.1089/108729001300338654

T. Samani, B. Jollès, A. Laigle

引用次数: 27

Nuclease resistance and RNase H sensitivity of oligonucleotides bridged by oligomethylenediol and oligoethylene glycol linkers. 低聚亚甲二醇和低聚乙二醇偶联的寡核苷酸的核酸酶抗性和RNase H敏感性。

Antisense & nucleic acid drug development Pub Date : 2001-04-01 DOI: 10.1089/108729001750171290

P. Vorobjev, I. Pyshnaya, D. V. Pyshnyi, A. Venyaminova, E. M. Ivanova, V. Zarytova, G. Bonora, C. Scalfi-happ, H. Seliger

{"title":"Nuclease resistance and RNase H sensitivity of oligonucleotides bridged by oligomethylenediol and oligoethylene glycol linkers.","authors":"P. Vorobjev, I. Pyshnaya, D. V. Pyshnyi, A. Venyaminova, E. M. Ivanova, V. Zarytova, G. Bonora, C. Scalfi-happ, H. Seliger","doi":"10.1089/108729001750171290","DOIUrl":"https://doi.org/10.1089/108729001750171290","url":null,"abstract":"The properties of new chimeric oligodeoxynucleotides made of short sequences (tetramers, pentamers, octamers, and decamers) bridged by hexamethylenediol and hexaethylene glycol linkers have been investigated. These chimeric oligonucleotides showed an improved resistance toward snake venom 3'-phosphodiesterase, with an increased stability when a terminal 3'-3'-internucleotide phosphodiester bond is present. It also has been demonstrated that the hybrid complexes formed by bridged oligonucleotides and a complementary 20-mer RNA are able to elicit the activity of ribonuclease H (RNase H) from Escherichia coli. The substrate properties of chimeric oligonucleotides depend on the length of the oligonucleotide fragments bridged by linkers. Introduction of a nonnucleotide spacer into the native oligonucleotide only slightly hampers the extent of the RNA hydrolysis in the hybrid complexes, whereas a modification of the site of reaction is observed as a possible consequence of the steric disturbance due to the aliphatic linkers. Hence, these new chimeric oligonucleotides, namely, short oligonucleotide fragments bridged by nonnucleotide linkers, demonstrate a favorable combination of exonuclease resistance and high substrate activity toward RNase H. As a consequence, these chimeric oligonucleotides could be proposed as new, promising analogs to be used in the antisense strategy.","PeriodicalId":7996,"journal":{"name":"Antisense & nucleic acid drug development","volume":"42 1","pages":"77-85"},"PeriodicalIF":0.0,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77815765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Propynylated phosphodiester oligonucleotides inhibit ICAM-1 expression in A549 cells on electroporation. 丙基化磷酸二酯寡核苷酸通过电穿孔抑制A549细胞中ICAM-1的表达。

Antisense & nucleic acid drug development Pub Date : 2001-04-01 DOI: 10.1089/108729001750171371

L. Meunier, M. Monsigny, A. Roche

引用次数: 3

Evidence for higher-order structure formation by the c-myb 18-mer phosphorothioate antisense (codons 2-7) oligodeoxynucleotide: potential relationship to antisense c-myb inhibition. c-myb 18聚硫代反义(密码子2-7)寡脱氧核苷酸形成高阶结构的证据:与反义c-myb抑制的潜在关系。

Antisense & nucleic acid drug development Pub Date : 2001-04-01 DOI: 10.1089/108729001750171317

M. Vilenchik, L. Benimetsky, A. Kolbanovsky, P. Miller, C. Stein

{"title":"Evidence for higher-order structure formation by the c-myb 18-mer phosphorothioate antisense (codons 2-7) oligodeoxynucleotide: potential relationship to antisense c-myb inhibition.","authors":"M. Vilenchik, L. Benimetsky, A. Kolbanovsky, P. Miller, C. Stein","doi":"10.1089/108729001750171317","DOIUrl":"https://doi.org/10.1089/108729001750171317","url":null,"abstract":"We have demonstrated the formation of higher-order structures (presumably tetraplexes) by an 18-mer phosphorothioate antisense c-myb oligodeoxyribonucleotide that has been shown to have activity in the treatment of leukemia xenograft models. Although not observable by conventionally employed techniques, such as PAGE and dimethyl sulfate (DMS) protection, the formation of such higher-order structures by this oligonucleotide was revealed by several techniques. These included capillary gel electrophoresis (CGE), which demonstrated the presence of molecules with greatly increased retention time compared with the monomer; magnetic circular dichroism spectroscopy, which demonstrated a band at 290 nm, a characteristic of antiparallel tetraplexes; and fluorescence energy transfer measurements. For the last, the 18-mer phosphorothioate oligonucleotide was synthesized with a 5'-fluorescein group. Similar to the molecular beacon model, its fluorescence was quenched when combined in solution with tetraplex-forming oligomers that contained a 3'-Dabcyl moiety. 7-Deazaguanosine inhibits the formation of tetraplexes by eliminated Hoogsteen base pair interactions. The wild-type and 7-deazaguanosine-substituted antisense c-myb oligomers differentially downregulated the expression of the c-myb proto-oncogene in K562 and HL60 cells, with the wild-type oligomer being the least active. The 18-mer c-myb molecule can, therefore, form highly complex structures, whose analysis in solution cannot be limited to examination of slab gel electrophoresis results alone.","PeriodicalId":7996,"journal":{"name":"Antisense & nucleic acid drug development","volume":"15 1","pages":"87-97"},"PeriodicalIF":0.0,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73513736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Optimization of hammerhead ribozymes for the cleavage of S100A4 (CAPL) mRNA. 双锤头核酶切割S100A4 (CAPL) mRNA的优化。

Antisense & nucleic acid drug development Pub Date : 2001-04-01 DOI: 10.1089/108729001750171272

E. Hovig, G. Maelandsmo, T. Mellingsaeter, O. Fodstad, S. Mielewczyk, J. Wolfe, J. Goodchild

{"title":"Optimization of hammerhead ribozymes for the cleavage of S100A4 (CAPL) mRNA.","authors":"E. Hovig, G. Maelandsmo, T. Mellingsaeter, O. Fodstad, S. Mielewczyk, J. Wolfe, J. Goodchild","doi":"10.1089/108729001750171272","DOIUrl":"https://doi.org/10.1089/108729001750171272","url":null,"abstract":"Previously, suppression of the S100A4 mRNA by an endogenously expressed ribozyme in osteosarcoma cells was shown to inhibit their metastasis in rats. As a prelude to performing similar studies with exogenous, synthetic ribozymes, we compared a series of hammerhead ribozymes targeted against different sites in the mRNA. The ribozymes differed only in the 7-base flanking sequences complementary to the substrate and were protected against nucleases by chemical modification. Cleavage efficiency varied widely and was not obviously related to the predicted secondary structure of the target RNA. The most active ribozyme of the series was chosen for further optimization. Lengthening its flanking sequences was counterproductive and reduced cleavage even when using excess ribozyme. Using excess substrate (multiple-turnover kinetics), cleavage was fastest with the (6+8) ribozyme having 6 nucleotides (nt) in stem III and 8 nt in stem I. Although these stems strongly influence ribozyme performance, their optimization is still empirical. Faster cleavage was obtained by adding facilitator oligonucleotides to ribozymes with shorter stems of (6+6) and (5+5) nt. Stimulation was particularly strong in the case of the (5+5) ribozyme, which was poorly active by itself. The enhancement caused by different facilitator oligonucleotides paralleled their expected ability to hybridize to RNA as a function of length and chemical modification.","PeriodicalId":7996,"journal":{"name":"Antisense & nucleic acid drug development","volume":"132 1 1","pages":"67-75"},"PeriodicalIF":0.0,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79618425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Antisense Editorial Office to Move 反义编辑部搬迁

Antisense & nucleic acid drug development Pub Date : 2001-04-01 DOI: 10.1089/108729001750171254

A. Krieg

{"title":"Antisense Editorial Office to Move","authors":"A. Krieg","doi":"10.1089/108729001750171254","DOIUrl":"https://doi.org/10.1089/108729001750171254","url":null,"abstract":"FOR THE LAST DECADE, the editorial office of the Antisense & Nucleic Acid Drug Development journal has been at the University of Iowa. During this time, the antisense field has undergone dramatic development, capped by the approval of the first antisense drug by the Food and Drug Administration and by the progressive increase in the number of antisense oligonucleotides used in human clinical trials. Some of these other antisense oligonucleotides are currently in phase III human clinical trials and seem likely to be approved by the FDA within the next few years. In addition to antisense oligonucleotides, therapeutic oligonucleotides that work through nonantisense mechanisms have also entered the clinic. Immune stimulatory oligonucleotides with CpG motifs are currently being evaluated in more than ten human clinical trials as immune activators for treatment or prevention of infectious diseases, cancer, and allergies. In order to promote the further clinical development of these CpG oligos, I will be taking a leave of absence from the University of Iowa and moving to Boston to join the Coley Pharmaceutical Group which is seeking to commercialize CpG technology. I will continue to run the editorial office of Antisense & Nucleic Acid Drug Development from the Coley Pharmaceutical Group headquarters. For our readers, there should be no apparent change in the functioning of the journal. However, we ask our authors and reviewers to note the new address of the editorial office and to make sure that correspondence and manuscripts are sent to this new address, effective immediately. It is: 93 Worcester Street, Suite 101, Wellesley, MA 02481. The phone number is: (781) 431-6400. The fax number is: (781) 4316403. The e-mail address is: akrieg@coleypharma.com We trust that the next decade of Antisense & Nucleic Acid Drug Development will be even more exciting than the last one!","PeriodicalId":7996,"journal":{"name":"Antisense & nucleic acid drug development","volume":"396 ","pages":"65-65"},"PeriodicalIF":0.0,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91452250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ADAM17 but not ADAM10 mediates tumor necrosis factor-alpha and L-selectin shedding from leukocyte membranes. ADAM17介导肿瘤坏死因子- α和l -选择素从白细胞膜脱落，而ADAM10不介导。

Antisense & nucleic acid drug development Pub Date : 2001-04-01 DOI: 10.1089/108729001750171353

T. Condon, S. Flournoy, Glenn J. Sawyer, B. Baker, T. Kishimoto, C. Bennett

引用次数: 79

Safety of intracoronary administration of c-myc antisense oligomers after percutaneous transluminal coronary angioplasty (PTCA). 经皮冠状动脉腔内成形术(PTCA)后冠状动脉内给药c-myc反义低聚物的安全性。

Antisense & nucleic acid drug development Pub Date : 2001-04-01 DOI: 10.1089/108729001750171335

F. Roque, G. Mon, J. Belardi, A. Rodríguez, L. Grinfeld, R. Long, S. Grossman, A. Malcolm, G. Zon, M. Ormont, D. Fischman, Y. Shi, A. Zalewski

{"title":"Safety of intracoronary administration of c-myc antisense oligomers after percutaneous transluminal coronary angioplasty (PTCA).","authors":"F. Roque, G. Mon, J. Belardi, A. Rodríguez, L. Grinfeld, R. Long, S. Grossman, A. Malcolm, G. Zon, M. Ormont, D. Fischman, Y. Shi, A. Zalewski","doi":"10.1089/108729001750171335","DOIUrl":"https://doi.org/10.1089/108729001750171335","url":null,"abstract":"We wished to assess the clinical safety and pharmacokinetics of ascending doses of a synthetic oligodeoxynucleotide (LR-3280) administered after coronary angioplasty. Antisense oligodeoxynucleotides designed to hybridize with target messenger ribonucleic acid (mRNA) in a complementary fashion to inhibit the expression of corresponding protein also have the ability to bind to extracellular growth factors. LR-3280 has been shown to reduce c-myc expression, inhibit growth and collagen biosynthesis in human vascular cells, and reduce neointimal formation in animal models of vascular injury. After successful percutaneous transluminal coronary angioplasty (PTCA), 78 patients were randomized to receive either standard care (n = 26) or standard care and escalating doses of LR-3280 (n = 52) (doses from 1 to 24 mg), administered into target vessel through a guiding catheter. Overall safety was evaluated by clinical adverse events, laboratory tests, and electrocardiograms. Patency was evaluated by quantitative coronary angiography. There were no clinically significant differences between treated and control patients. No adverse effects of LR-3280 on the patency of dilated coronary arteries were observed. Pharmacokinetic data revealed that peak plasma concentrations of LR-3280 occurred at 1 minute over the studied dose range and rapidly decreased after approximately1 hour, with little LR-3280 detected in the urine between 0-6 hours and 12-24 hours. The intracoronary administration of LR-3280 is well tolerated at doses up to 24 mg and produces no adverse effects in dilated coronary arteries. These results provide the basis for the evaluation of local delivery of this phosphorothioate oligodeoxynucleotide for the prevention of human vasculoproliferative disease.","PeriodicalId":7996,"journal":{"name":"Antisense & nucleic acid drug development","volume":"63 1","pages":"99-106"},"PeriodicalIF":0.0,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77620566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 14