Abstract:
:We have previously identified a target site in HIV-1 RNA that was particularly accessible to a ribozyme and a short hairpin RNA (shRNA). To design small interfering RNAs (siRNAs) targeting this site, we evaluated the effects of siRNAs with different lengths on HIV-1 production. The potency and efficacy of these siRNAs were dependent on the length of their intended sense strand with trends for symmetrical and asymmetrical formats that were similar. Although a typical canonical format with a 21-nucleotide (nt) sense strand was effective at inhibiting HIV-1 production, Dicer substrate siRNAs (dsiRNAs) with the longest lengths (27 to 29 nucleotides) were the most effective. Induction of double-stranded RNA immune responses and effects on cell viability were not detected in cells transfected with different siRNAs, suggesting that the differences observed were not related to indirect effects on HIV-1 production. For the corresponding shRNA designs, a different trend in potency and efficacy against HIV-1 production was observed, with the most effective shRNAs having stem lengths from 20 to 27 bp. Our results highlight the importance of evaluating different designs to identify the best siRNA and shRNA formats for any particular target site and provide a set of highly effective molecules for further development as drug and gene therapies for HIV-1 infection.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Scarborough RJ,Adams KL,Daher A,Gatignol Adoi
10.1128/AAC.00949-15subject
Has Abstractpub_date
2015-09-01 00:00:00pages
5297-305issue
9eissn
0066-4804issn
1098-6596pii
AAC.00949-15journal_volume
59pub_type
杂志文章abstract::Recent studies using laboratory clones have demonstrated that several antiretroviral protease inhibitors (PIs) inhibit the growth of Plasmodium falciparum at concentrations that may be of clinical significance, especially during human immunodeficiency virus type 1 (HIV-1) and malaria coinfection. Using clinical isolat...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.00169-08
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abstract::Early studies of immobilized peptides mainly focused upon the relationship between structural properties and the activity of soluble and surface-tethered sequences. The intention of this study was to analyze the influence of immobilization parameters upon the activity profile of peptides. Resin beads (TentaGel S NH(2)...
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doi:10.1128/AAC.01254-08
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abstract::Multidrug resistance in Gram-negative bacteria has become so threatening to human health that new antibacterial platforms are desperately needed to combat these deadly infections. The concept of siderophore conjugation, which facilitates compound uptake across the outer membrane by hijacking bacterial iron acquisition...
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doi:10.1128/AAC.00629-13
更新日期:2013-09-01 00:00:00
abstract::We investigated the impact of the piperacillin-tazobactam MIC in the outcome of 39 bloodstream infections due to extended-spectrum-β-lactamase-producing Escherichia coli. All 11 patients with urinary tract infections survived, irrespective of the MIC. For other sources, 30-day mortality was lower for isolates with a M...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00135-13
更新日期:2013-07-01 00:00:00
abstract::Plasmid-mediated mechanisms, comprising TEM hyperproduction, TEM derivative production, and OXA production, lead to amoxicillin-clavulanic acid resistance in enterobacteria. The ability of the single-strand conformation polymorphism (SSCP)-PCR method to differentiate the genes encoding inhibitor-resistant beta-lactama...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.4.879
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abstract::This study investigates the role of active efflux system MexXY in the emergence of aminoglycoside (AG) resistance among cystic fibrosis (CF) isolates of Pseudomonas aeruginosa. Three genotypically related susceptible and resistant (S/R) bacterial pairs and three other AG-resistant CF strains were compared to four non-...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.48.5.1676-1680.2004
更新日期:2004-05-01 00:00:00
abstract::Intraoperative biliary cefamandole concentrations were determined in 16 patients with hepatobiliary pathology. These included seven patients with cholelithiasis, five with acute cholecystitis, two with recurrent ascending cholangitis, and two with liver abscesses. Bile collected 0.5 to 2.5 h after the last antibiotic ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.22.6.1087
更新日期:1982-12-01 00:00:00
abstract::Mercury has a long history as an antimicrobial agent effective against eukaryotic and prokaryotic organisms. Despite its prolonged use, the basis for mercury toxicity in prokaryotes is not well understood. Archaea, like bacteria, are prokaryotes but they use a simplified version of the eukaryotic transcription apparat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.6.1993-1999.2004
更新日期:2004-06-01 00:00:00
abstract::Tuberculosis (TB) treatment is long and requires multiple drugs, likely due to various phenotypes of TB bacilli with variable drug susceptibilities. Drugs with broad activity are urgently needed. This study aimed to evaluate delamanid's activity against growing or dormant bacilli in vitro as well as in vivo Cultures o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02402-16
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abstract::The Candida albicans CDR1 and CDR2 genes code for highly homologous ATP-binding cassette (ABC) transporters which are overexpressed in azole-resistant clinical isolates and which confer resistance to multiple drugs by actively transporting their substrates out of the cells. These transporters are formed by two homolog...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.5.1543-1554.2003
更新日期:2003-05-01 00:00:00
abstract::The exogenous control of hepatitis C virus (HCV) replication can be mediated through the inhibition of the RNA-dependent RNA polymerase (RdRp) activity of NS5B. Small-molecule inhibitors of NS5B include nucleoside and nonnucleoside analogs. Here, we report the discovery of a novel class of HCV polymerase nonnucleoside...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00669-08
更新日期:2008-12-01 00:00:00
abstract::Cefazolin was added to dialysis fluid in nine patients with renal failure undergoing peritoneal dialysis with 2 liters/h per exchange. With 50 mg/liter (three patients), the first measurable mean serum concentration was 3.7 mug/ml (range, 2.4 to 4.9 mug/ml) after three exchanges and was 30.3 mug/ml (range, 13.3 to 44....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.14.3.318
更新日期:1978-09-01 00:00:00
abstract::Nemonoxacin (TG-873870) is a novel nonfluorinated quinolone with potent broad-spectrum activity against Gram-positive, Gram-negative, and atypical pathogens, including vancomycin-nonsusceptible methicillin-resistant Staphylococcus aureus (MRSA), quinolone-resistant MRSA, quinolone-resistant Streptococcus pneumoniae, p...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.02972-14
更新日期:2014-10-01 00:00:00
abstract::To compare the effects of four antimicrobial peptides (MUC7 12-mer, histatin 12-mer, cathelicidin KR20, and a peptide containing lactoferricin amino acids 1 to 11) on the yeast Saccharomyces cerevisiae, we employed a genomewide fitness screen of combined collections of mutants with homozygous deletions of nonessential...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01439-12
更新日期:2013-02-01 00:00:00
abstract::The pharmacokinetics and protein binding of ceforanide were studied in 15 patients undergoing cholecystectomies. Each patient received ceforanide (20 mg/kg) intravenously on arrival in the operating room, after which serial blood samples were collected during the elimination phase for determination of total and free c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.27.4.487
更新日期:1985-04-01 00:00:00
abstract::Eleven patients about to undergo pulmonary surgery received a bolus injection of 1 g of cefoxitin. The concentrations of cefoxitin in the serum 1 and 2 h after dosage were 38.5 +/- 1.89 and 23.7 +/- 2.56 mug/ml; the lung concentrations at the respective times were 12.6 +/- 0.7 and 10.06 +/- 0.43 mug/ml. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.23.2.323
更新日期:1983-02-01 00:00:00
abstract::Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) isolates are increasingly migrating from livestock into human and animal health care settings. Alternative substances are needed to overcome the drawbacks of currently available drugs used for MRSA eradication. The recombinant bacteriophage end...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00385-18
更新日期:2018-06-26 00:00:00
abstract::Antimicrobial efficacy in orthopedic device infections is diminished because of bacterial biofilms which express tolerance to antibiotics. Recently, the use of high doses of levofloxacin with rifampin has been recommended for staphylococcal infections. In the present study, we evaluated the efficacy of levofloxacin at...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00523-06
更新日期:2006-12-01 00:00:00
abstract::Against 443 aerobic and anaerobic bacteria isolated from diabetic foot infections, ceftobiprole MICs (microg/ml) at which 90% of the isolates tested were inhibited were as follows: methicillin-resistant Staphylococcus aureus, 1; methicillin-susceptible S. aureus and Staphylococcus lugdunensis, 0.5; Anaerococcus prevot...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00722-06
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abstract::The in vitro activities of amphotericin B, itraconazole, fluconazole, voriconazole, posaconazole, and ravuconazole against 39 isolates of Trichosporon spp. were determined by the NCCLS M27-A microdilution method. The azoles tested appeared to be more potent than amphotericin B. Low minimal fungicidal concentration/MIC...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.46.4.1144-1146.2002
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abstract::Respiratory syncytial virus (RSV) causes serious illness (lower respiratory illness) in preterm infants. RSV antibody-enriched immunoglobulin (RSVIG) that was lyophilized (LYO) protected against RSV lower respiratory illness. The Food and Drug Administration now requires an additional viral inactivation step (VI). We ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1995-03-01 00:00:00
abstract::Pseudomonas aeruginosa clinical isolate CY-1, which was resistant to ceftazidime, harbored a conjugative ca. 250-kb plasmid that contained a class 1 integron with two gene cassettes encoding OXA-32, an OXA-2- type beta-lactamase, and the aminoglycoside acetyltransferase AAC(6')Ib(9). OXA-32 differed from OXA-2 by an L...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.2.566-569.2002
更新日期:2002-02-01 00:00:00
abstract::An a priori pharmacokinetic/pharmacodynamic (PK/PD) target of 40% daily time above the MIC (T >MIC; based on the MIC(90) of 0.06 microg/ml for Streptococcus pyogenes reported in the literature) was shown to be achievable in a phase 1 study of 23 children with a once-daily (QD) modified-release, multiparticulate formul...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2008-07-01 00:00:00
abstract::Efavirenz-based antiretroviral regimen is preferred during rifampin-containing tuberculosis therapy. However, current pharmacokinetic data are insufficient to guide optimized concurrent dosing. This study aimed to better characterize the effects of rifampin on efavirenz pharmacokinetics. Subjects were randomized to re...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/AAC.00980-10
更新日期:2011-07-01 00:00:00
abstract::The 18-amino-acid cationic, tryptophan-rich ApoEdpL-W peptide derived from human ApoE apolipoprotein was shown to have antifungal activity against pathogenic yeasts of the Candida genus (except C. glabrata). ApoEdpL-W was active against planktonic cells and early-stage biofilms but less active against mature biofilms,...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00319-11
更新日期:2011-10-01 00:00:00
abstract::The effectiveness of antibiotic treatment was examined in a mouse model of Lyme borreliosis. Mice were treated with ceftriaxone or saline solution for 1 month, commencing during the early (3 weeks) or chronic (4 months) stages of infection with Borrelia burgdorferi. Tissues from mice were tested for infection by cultu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01050-07
更新日期:2008-05-01 00:00:00
abstract::We evaluated the antituberculosis (anti-TB) activity of five β-lactams alone or in combination with β-lactamase inhibitors against 41 clinical isolates of Mycobacterium tuberculosis, including multidrug-resistant and extensively drug-resistant strains. Of those, tebipenem, an oral carbapenem, showed the most potent an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03539-14
更新日期:2014-11-01 00:00:00
abstract::Thirty-four infants and children ranging in age from 2.5 to 180 months (mean, 40 months) were treated with parenteral moxalactam (150 mg/kg per day) for suspected or proved bacterial infections outside the central nervous system. Six patients infected with Haemophilus influenzae b, nine infected with Staphylococcus au...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.6.898
更新日期:1982-06-01 00:00:00
abstract::The intrinsic mechanisms of resistance to beta-lactam antibiotics in Serratia marcescens IFO 12648 were investigated, comparing the action of benzylpenicillin, apalcillin, cefazolin, and ceftizoxime. The minimal inhibitory concentrations for this strain were 1,600, 3.13, 6,400, and 0.05 microgram/ml, respectively. The...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.19.3.397
更新日期:1981-03-01 00:00:00
abstract::The effect of protein binding on the activity of teicoplanin against Staphylococcus aureus was evaluated. Bactericidal rates of teicoplanin in cation-supplemented Mueller-Hinton broth (SMHB) and in a 1:1 mixture of pooled human serum and cation-supplemented Mueller-Hinton broth (PHS-SMHB) were compared with those of v...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/aac.35.6.1089
更新日期:1991-06-01 00:00:00