Antisense & nucleic acid drug development最新文献_第4页

A rapid and simple nonradioactive method for in vitro testing of ribozyme activity. 一种快速简便的体外检测核酶活性的无放射性方法。

Antisense & nucleic acid drug development Pub Date : 2002-08-01 DOI: 10.1089/108729002320351601

Riting Liu, Benjamin Rohe, Daniel D Carson, Mary C Farach-Carson

{"title":"A rapid and simple nonradioactive method for in vitro testing of ribozyme activity.","authors":"Riting Liu, Benjamin Rohe, Daniel D Carson, Mary C Farach-Carson","doi":"10.1089/108729002320351601","DOIUrl":"https://doi.org/10.1089/108729002320351601","url":null,"abstract":"Ribozymes that target specific messenger RNA transcripts are powerful tools in the emerging fields of functional genomics, proteomics, and metabolomics. We have found that successful in vitro testing greatly increases the likelihood of producing ribozymes with good efficacy in living cells. A rapid and simple nonradioactive method for systematic in vitro testing of ribozyme-cleaving activity is reported. Ribozymes are synthesized enzymatically from double-stranded DNA (dsDNA) oligonucleotides without vector cloning. Substrate target DNA template is cloned into a vector flanked with SP6 and T7 promoters at multiple cloning sites that permit colorimetric screening and ampicillin selection, enhancing the efficiency of the cloning procedure. Ribozyme cleavage products are satisfactorily resolved on 2.0% NuSieve 3:1 agarose (FMC Products, Rockland, ME)/formaldehyde gels by electrophoresis. This method avoids the preparation of polyacrylamide gels. Using this procedure, the ribozyme, target substrate RNA, and ribozyme cleavage products are all easily detected by ethidium bromide staining. Resolution and detection are fast and simple, eliminating the need for either polyacrylamide gel analysis or radiolabeling. The use of RNase inhibitors in the assays is also assessed and discussed.","PeriodicalId":7996,"journal":{"name":"Antisense & nucleic acid drug development","volume":"12 4","pages":"283-8"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/108729002320351601","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21997892","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: 10

Direct measurement of the association constant of HER2/neu antisense oligonucleotide to its target RNA sequence using a molecular beacon. 使用分子信标直接测量HER2/ new反义寡核苷酸与其靶RNA序列的关联常数。

Antisense & nucleic acid drug development Pub Date : 2002-08-01 DOI: 10.1089/108729002320351548

Veena Vijayanathan, Thresia Thomas, Leonard H Sigal, T J Thomas

{"title":"Direct measurement of the association constant of HER2/neu antisense oligonucleotide to its target RNA sequence using a molecular beacon.","authors":"Veena Vijayanathan, Thresia Thomas, Leonard H Sigal, T J Thomas","doi":"10.1089/108729002320351548","DOIUrl":"https://doi.org/10.1089/108729002320351548","url":null,"abstract":"A molecular beacon approach was developed to directly determine the association constant of RNA-DNA hybrid formation. The molecular beacon was composed of a 15-nt loop structure containing the antisense sequence that can hybridize with the AUG translational start site of the HER2/neu gene, which is overexpressed in a significant proportion of breast, ovarian, and lung tumors. The equilibrium association constant (Ka) of DNA binding to the RNA oligonucleotide was 6.4 +/- 0.14 x 10(7) M(-1) in the presence of 150 mM NaCl at 22 degrees C. The free energy change (AG) associated with RNA-DNA hybrid formation was -10.7 kcal/mole. The melting temperature (Tm) of RNA-DNA hybrid was 64.4 degrees C +/- 1 degree C in the presence of 150 mM NaCl. The RNA-DNA hybrid was more stable than the corresponding DNA-DNA duplex in 150 mM NaCl, as judged by both Ka and Tm data. We also determined the Ka, deltaG, and Tm values of RNA-DNA and DNA-DNA duplex formation in the presence of three monovalent cations, Li+, K+, and Cs+. The feasibility of this method was also investigated using a phosphorothioate molecular beacon. The information generated through this new approach for thermodynamic measurements might be useful for the design of oligonucleotides for antisense therapeutics.","PeriodicalId":7996,"journal":{"name":"Antisense & nucleic acid drug development","volume":"12 4","pages":"225-33"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/108729002320351548","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21997886","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: 20

In vitro selection of DNA aptamers against the HIV-1 TAR RNA hairpin. 抗HIV-1 TAR RNA发夹DNA适体的体外筛选。

Antisense & nucleic acid drug development Pub Date : 2002-08-01 DOI: 10.1089/108729002320351584

Dalila Sekkai, Eric Dausse, Carmelo Di Primo, Fabien Darfeuille, Claudine Boiziau, Jean-Jacques Toulmé

{"title":"In vitro selection of DNA aptamers against the HIV-1 TAR RNA hairpin.","authors":"Dalila Sekkai, Eric Dausse, Carmelo Di Primo, Fabien Darfeuille, Claudine Boiziau, Jean-Jacques Toulmé","doi":"10.1089/108729002320351584","DOIUrl":"https://doi.org/10.1089/108729002320351584","url":null,"abstract":"In vitro selection was performed to identify DNA aptamers against the TAR RNA stem-loop structure of HIV-1. A counterselection step allowed the elimination of kissing complex-forming aptamers previously selected (Boiziau et al. J. Biol. Chem. 1999; 274:12730). This led to the emergence of oligonucleotides, most of which contained two consensus sequences, one targeted to the stem 3'-strand (5'-CCCTAGTTA) and the other complementary to the TAR apical loop (5'-CTCCC). The best aptamer could be shortened to a 19-mer oligonucleotide, characterized by a dissociation constant of 50 nM. A 16-mer oligonucleotide complementary to the TAR stem 3'-strand could also be derived from the identified aptamers, with an equal affinity (Kd = 50 nM). Experiments performed to elucidate the interaction between TAR and the aptamers (UV melting measures, enzymatic and chemical footprints) demonstrated that the TAR stem 5'-strand was not simply displaced as a result of the complex formation but unexpectedly remained associated on contact with the antisense oligonucleotide. We suggest that a multistranded structure could be formed.","PeriodicalId":7996,"journal":{"name":"Antisense & nucleic acid drug development","volume":"12 4","pages":"265-74"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/108729002320351584","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21997890","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: 24

Nuclear extracts promote gene correction and strand pairing of oligonucleotides to the homologous plasmid. 核提取物促进基因校正和与同源质粒的寡核苷酸链配对。

Antisense & nucleic acid drug development Pub Date : 2002-08-01 DOI: 10.1089/108729002320351557

Olga Igoucheva, Vitali Alexeev, Kyonggeun Yoon

{"title":"Nuclear extracts promote gene correction and strand pairing of oligonucleotides to the homologous plasmid.","authors":"Olga Igoucheva, Vitali Alexeev, Kyonggeun Yoon","doi":"10.1089/108729002320351557","DOIUrl":"https://doi.org/10.1089/108729002320351557","url":null,"abstract":"We compared strand pairing and gene correction activities between different constructs of oligonucleotides, using homologous supercoiled DNA and eukaryotic nuclear extracts. The RNA-DNA chimeric oligonucleotide was more efficient in strand pairing and gene correction than its DNA-DNA homolog. Single-stranded deoxyoligonucleotides showed similar strand pairing and correction activity to the modified RNA-DNA chimeric oligonucleotides, whereas single-stranded ribooligonucleotides did not show either activity. However, the correlations were not always linear, suggesting that only a fraction of the joint molecules may be processed to cause the final gene correction. Several mammalian extracts with markedly different in vitro activity showed the similar amounts of the joint molecules. These results led us to conclude that strand pairing is a necessary event in gene correction but may not be the rate-limiting step. Furthermore, depletion of HsRad51 protein caused large decreases in both strand-pairing and functional activities, whereas supplementation of HsRad51 produced only a slight increase in the repair activity, indicating that HsRad51 participates in the strand pairing, but subsequent steps define the frequency of gene correction. In addition, we found that the structure and stability of intermediates formed by single-stranded deoxyoligonucleotides and RNA-DNA chimeric oligonucleotides were different, suggesting that they differ in their mechanisms of gene repair.","PeriodicalId":7996,"journal":{"name":"Antisense & nucleic acid drug development","volume":"12 4","pages":"235-46"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/108729002320351557","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21997887","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: 27

Increase in therapeutic index of doxorubicin and vinblastine by aptameric oligonucleotide in human T lymphoblastic drug-sensitive and multidrug-resistant cells. 多柔比星和长春花碱对人T淋巴细胞药敏和多重耐药细胞治疗指数的影响。

Antisense & nucleic acid drug development Pub Date : 2002-08-01 DOI: 10.1089/108729002320351566

Barbara Dapas, Laura Perissin, Carlo Pucillo, Franco Quadrifoglio, Bruna Scaggiante

{"title":"Increase in therapeutic index of doxorubicin and vinblastine by aptameric oligonucleotide in human T lymphoblastic drug-sensitive and multidrug-resistant cells.","authors":"Barbara Dapas, Laura Perissin, Carlo Pucillo, Franco Quadrifoglio, Bruna Scaggiante","doi":"10.1089/108729002320351566","DOIUrl":"https://doi.org/10.1089/108729002320351566","url":null,"abstract":"Aptameric GT oligomers are a new class of potential anticancer molecules that inhibit the growth of human cancer cell lines by binding to specific nuclear proteins. We demonstrated that an aptameric GT oligonucleotide increased the therapeutic index of doxorubicin and vinblastine in T lymphoblastic drug-sensitive and multidrug-resistant (MDR) cells. The doxorubicin ID50 decreased 6.5-fold by coadministration of 1 microM GT to CCRF-CEM cells and by 24-fold by coadministration of 0.75 microM GT to CEM-VLB300 cells. In CEM-VLB300 cells, the vinblastine ID50 decreased 11-fold by coadministration of 0.5 microM GT. Control CT sequence did not potentiate the drugs in either CCRF-CEM or CEM-VLB300 cells. The ability of GT to bind to specific nuclear proteins in cancer cells related to the increase in the therapeutic index of doxorubicin and vinblastine. No cooperation was detected by the administration of GT oligomer together with doxorubicin to rat differentiated thyroid FRTL-5 cells and to normal human lymphocytes. These cells did not show binding of GT to the specific nuclear proteins, and they were not sensitive to the cytotoxic action of the GT sequence. Drug potentiation by GT not involving normal human lymphocytes might be exploited to develop a more selective treatment of drug-sensitive and MDR tumors.","PeriodicalId":7996,"journal":{"name":"Antisense & nucleic acid drug development","volume":"12 4","pages":"247-55"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/108729002320351566","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21997888","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: 11

Intracellular inhibition of hepatitis B virus S gene expression by chimeric DNA-RNA phosphorothioate minimized ribozyme. 嵌合DNA-RNA硫代最小化核糖酶抑制乙型肝炎病毒S基因表达的研究。

Antisense & nucleic acid drug development Pub Date : 2002-08-01 DOI: 10.1089/108729002320351575

Theresa May Chin Tan, Lei Zhou, Sandrine Houssais, Bee Leng Seet, Stephan Jaenicke, Frank Peter, Seng Gee Lim

{"title":"Intracellular inhibition of hepatitis B virus S gene expression by chimeric DNA-RNA phosphorothioate minimized ribozyme.","authors":"Theresa May Chin Tan, Lei Zhou, Sandrine Houssais, Bee Leng Seet, Stephan Jaenicke, Frank Peter, Seng Gee Lim","doi":"10.1089/108729002320351575","DOIUrl":"https://doi.org/10.1089/108729002320351575","url":null,"abstract":"Chronic hepatitis B virus (HBV) infection is a major problem in Asia. Current therapies for chronic hepatitis B have limited efficacy. The successful use of ribozymes for intracellular inhibition of HBV gene expression was recently reported. As an alternative to ribozymes, the use of DNA-containing, phosphorothioate-modified, minimized hammerhead ribozymes (minizymes) to inhibit hepatitis B surface antigen (HBsAg) expression and viral replication was investigated. Such molecules can be synthesized and supplied exogenously. Two conserved sites within the HBsAg open reading frame (ORF) were targeted. PLC/PRF5 cells or 2.2.15 cells were treated with minizymes or antisense oligomers to assess the effects on cell viability, HBsAg expression, and viral DNA production. Treatment with the minizyme, MZPS1, resulted in >80% inhibition of HBsAg expression in PLC/PRF5 cells. MZPS1 had more inhibitory effect than the antisense oligonucletoide target at the same region, whereas the control minizyme had little effect. Another gene-specific minizyme, MZPS2, did not show any effect. Treated cells remained fully viable. Treatment of 2.2.15 cells with MZPS1 also led to decreased HBsAg expression. In addition, a 2.3-fold decrease in viral production was observed. Our data showed that minizymes can inhibit HBV gene expression and may potentially be useful for clinical therapy against chronic HBV infection.","PeriodicalId":7996,"journal":{"name":"Antisense & nucleic acid drug development","volume":"12 4","pages":"257-64"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/108729002320351575","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21997889","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: 11

A molecular beacon strategy for real-time monitoring of triplex DNA formation kinetics. 实时监测三重DNA形成动力学的分子信标策略。

Antisense & nucleic acid drug development Pub Date : 2002-06-01 DOI: 10.1089/108729002760220743

T. Antony, V. Subramaniam

{"title":"A molecular beacon strategy for real-time monitoring of triplex DNA formation kinetics.","authors":"T. Antony, V. Subramaniam","doi":"10.1089/108729002760220743","DOIUrl":"https://doi.org/10.1089/108729002760220743","url":null,"abstract":"We used a molecular beacon (MB) containing a 15-mer triplex-forming oligonucleotide (TFO) to probe in real-time the kinetics of triplex DNA formation in the left side of the TCl tract (502-516) of the c-src proto-oncogene in vitro. The metal ions Na+, K+, and Mg2+ stabilized triplex DNA at this site. The pseudo-first-order rate constant (kpsi) and the second-order association rate constant (k1) for the binding of the MB to the target duplex in 10 mM sodium phosphate buffer, pH 7.3, increased from 3.2 +/- 0.9 to 15 +/- 2.8 x 10(-3) s(-1) and 6.4 +/- 1.8 to 30 +/- 5.6 x 102 M(-1) s(-1), respectively, on increasing the MgCl2 concentration from 1 to 2.5 mM. Similar values were obtained for the triplex DNA stabilized by NaCl (100-250 mM). Surprisingly, the values were around 2 times higher in the presence of KCl. The AG of triplex formation in the presence of 1 mM MgCl2, 150 mM NaCl, and 150 mM KCl were -7.8 +/- 0.3, -8.2 +/- 0.3 and -8.7 +/- 0.7 kcal/mol respectively, despite significant differences in the values of deltaH and deltaS, suggesting enthalpy-entropy compensation in the stabilization of the triplex DNA by these metal ions. These results show the utility of MBs ih probing triplex DNA formation and in evaluating kinetic and thermodynamic parameters important for the design and development of TFOs as triplex DNA-based therapeutic agents.","PeriodicalId":7996,"journal":{"name":"Antisense & nucleic acid drug development","volume":"41 1","pages":"145-54"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83739538","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: 17

Discovery and development of respirable antisense therapeutics for asthma. 呼吸性反义哮喘治疗药物的发现与发展。

Antisense & nucleic acid drug development Pub Date : 2002-06-01 DOI: 10.1089/108729002760220770

A. Sandrasagra, S. Leonard, Lei Tang, K. Teng, Yukui Li, H. Ball, J. Mannion, J. Nyce

{"title":"Discovery and development of respirable antisense therapeutics for asthma.","authors":"A. Sandrasagra, S. Leonard, Lei Tang, K. Teng, Yukui Li, H. Ball, J. Mannion, J. Nyce","doi":"10.1089/108729002760220770","DOIUrl":"https://doi.org/10.1089/108729002760220770","url":null,"abstract":"Respirable antisense oligonucleotides (RASONs) represent a novel class of respiratory therapeutic molecules with the potential to specifically address the challenges posed by the successes of the Human Genome Program, namely, the need to rapidly identify the critical pulmonary disease-relevant drugable targets from the vast pool of 30,000-40,000 human genes and to discover and develop drugs that specifically attack these targets. We have shown that EPI-2010, a RASON targeting the adenosine A1 receptor, a G-protein coupled receptor that has been implicated in the regulation of three major determinants of asthma, can be delivered directly to the target disease tissue as an aerosol formulation. In vivo efficacy, absorption, distribution, metabolism, and excretion (ADME), and safety studies of inhaled EPI-2010 employing animal models of human asthma suggest that the RASON approach enables the specific delivery of efficacious, safe, and long-acting doses of phosphorothioate oligonucleotides to the respiratory tract. Moreover, these data indicate that RASONs truly have the potential to address the respiratory drug discovery bottleneck of the postgenomic era, that is, the ability to rapidly validate disease targets and develop pulmonary disease therapeutics for these validated targets.","PeriodicalId":7996,"journal":{"name":"Antisense & nucleic acid drug development","volume":"16 1","pages":"177-81"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88507830","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: 32

GeneBlocs are powerful tools to study and delineate signal transduction processes that regulate cell growth and transformation. 基因块是研究和描述调节细胞生长和转化的信号转导过程的有力工具。

Antisense & nucleic acid drug development Pub Date : 2002-06-01 DOI: 10.1089/108729002760220734

Maria Sternberger, A. Schmiedeknecht, A. Kretschmer, F. Gebhardt, F. Leenders, Frank Czauderna, I. von Carlowitz, M. Engle, K. Giese, L. Beigelman, A. Klippel

{"title":"GeneBlocs are powerful tools to study and delineate signal transduction processes that regulate cell growth and transformation.","authors":"Maria Sternberger, A. Schmiedeknecht, A. Kretschmer, F. Gebhardt, F. Leenders, Frank Czauderna, I. von Carlowitz, M. Engle, K. Giese, L. Beigelman, A. Klippel","doi":"10.1089/108729002760220734","DOIUrl":"https://doi.org/10.1089/108729002760220734","url":null,"abstract":"The study of signal transduction processes using antisense oligonucleotides is often complicated by low intracellular stability of the antisense reagents or by nonspecific effects that cause toxicity. Here, we introduce a new class of antisense molecules, so-called GeneBlocs, which are characterized by improved stability, high target RNA specificity, and low toxicity. GeneBlocs allow for efficient downregulation of mRNA expression at nanomolar concentrations, and they do not interfere with cell proliferation. We demonstrate these beneficial properties using a positive readout system. GeneBloc-mediated inhibition of tumor suppressor PTEN (phosphatase and tension homologue detected on chromosome 10) expression leads to hyperactivation of the phosphatidylinositol (PI) 3-kinase pathway, thereby mimicking the loss of PTEN function and its early consequences observed in mammalian cancer cells. Specifically, cells treated with PTEN GeneBlocs show functional activation of Akt, a downstream effector of PI 3-kinase signaling, and exhibit enhanced proliferation when seeded on a basement membrane matrix. In addition, GeneBlocs targeting the catalytic subunit of PI 3-kinase, p110, specifically inhibit signal transduction of endogenous or recombinant PI 3-kinase. This demonstrates that GeneBlocs are powerful tools to analyze and to modulate signal transduction processes and, therefore, represent alternative reagents for the validation of gene function.","PeriodicalId":7996,"journal":{"name":"Antisense & nucleic acid drug development","volume":"54 1","pages":"131-43"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80186265","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: 34

A Special Issue: The Commercial Development of Nucleic Acids 特刊:核酸的商业发展

Antisense & nucleic acid drug development Pub Date : 2002-06-01 DOI: 10.1089/108729002760220725

A. Krieg, C. Stein, C. Bennett

引用次数: 0