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Total 63 results found since Jan 2013.

The reverse transcriptase–RNase H: from viruses to antiviral defense
Ubiquitous, reverse transcriptase may have contributed to the transition from the RNA to the DNA world, a transition that also involved RNase H–like activities. Both enzymes shaped various genomes and antiviral defense systems as endogenous retroviruses (ERVs) and transposable elements (TEs). A close relationship between a dozen components of retroviruses and the small interfering RNA (siRNA) antiviral‐defense machinery has been characterized. Most antiviral‐defense systems involve RNase H–like enzymes destroying invading nucleic acids, RNA, or DNA. Such enzymes include RNases H, Argonaute, Dicer, Cas9, transposase...
Source: Annals of the New York Academy of Sciences - February 19, 2015 Category: Science Authors: Karin Moelling, Felix Broecker Tags: Original Article Source Type: research

Protein kinase IKK{beta} activates IRF5 Biochemistry
The siRNA knockdown of IFN Regulatory Factor 5 (IRF5) in the human plasmacytoid dendritic cell line Gen2.2 prevented IFNβ production induced by compound CL097, a ligand for Toll-like receptor 7 (TLR7). CL097 also stimulated the phosphorylation of IRF5 at Ser462 and stimulated the nuclear translocation of wild-type IRF5, but not...
Source: Proceedings of the National Academy of Sciences - December 9, 2014 Category: Science Authors: Lopez-Pelaez, M., Lamont, D. J., Peggie, M., Shpiro, N., Gray, N. S., Cohen, P. Tags: Biological Sciences Source Type: research

Satellite siRNA promotes Drosophila X recognition Genetics
Highly differentiated sex chromosomes create a lethal imbalance in gene expression in one sex. To accommodate hemizygosity of the X chromosome in male fruit flies, expression of X-linked genes increases twofold. This is achieved by the male- specific lethal (MSL) complex, which modifies chromatin to increase expression. Mutations that disrupt...
Source: Proceedings of the National Academy of Sciences - November 18, 2014 Category: Science Authors: Menon, D. U., Coarfa, C., Xiao, W., Gunaratne, P. H., Meller, V. H. Tags: Biological Sciences Source Type: research

Correlating animal and human data with CALAA-01 Medical Sciences
Nanoparticle-based experimental therapeutics are currently being investigated in numerous human clinical trials. CALAA-01 is a targeted, polymer-based nanoparticle containing small interfering RNA (siRNA) and, to our knowledge, was the first RNA interference (RNAi)–based, experimental therapeutic to be administered to cancer patients. Here, we report the results from the initial phase...
Source: Proceedings of the National Academy of Sciences - August 5, 2014 Category: Science Authors: Zuckerman, J. E., Gritli, I., Tolcher, A., Heidel, J. D., Lim, D., Morgan, R., Chmielowski, B., Ribas, A., Davis, M. E., Yen, Y. Tags: Biological Sciences Source Type: research

Stability of siRNA on nanoparticle constructs Chemistry
Small interfering RNA (siRNA) is a powerful and highly effective method to regulate gene expression in vitro and in vivo. However, the susceptibility to serum nuclease-catalyzed degradation is a major challenge and it remains unclear whether the strategies developed to improve the stability of siRNA free in serum solution are...
Source: Proceedings of the National Academy of Sciences - July 8, 2014 Category: Science Authors: Barnaby, S. N., Lee, A., Mirkin, C. A. Tags: Physical Sciences Source Type: research

RPL39, MLF2 alter tumor initiation and metastasis Cell Biology
We previously described a gene signature for breast cancer stem cells (BCSCs) derived from patient biopsies. Selective shRNA knockdown identified ribosomal protein L39 (RPL39) and myeloid leukemia factor 2 (MLF2) as the top candidates that affect BCSC self-renewal. Knockdown of RPL39 and MLF2 by specific siRNA nanoparticles in patient-derived and...
Source: Proceedings of the National Academy of Sciences - June 17, 2014 Category: Science Authors: Dave, B., Granados-Principal, S., Zhu, R., Benz, S., Rabizadeh, S., Soon-Shiong, P., Yu, K.-D., Shao, Z., Li, X., Gilcrease, M., Lai, Z., Chen, Y., Huang, T. H.- M., Shen, H., Liu, X., Ferrari, M., Zhan, M., Wong, S. T. C., Kumaraswami, M., Mittal, V., Ch Tags: Biological Sciences Source Type: research

Correction for Dong et al., Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates Correction
ENGINEERING Correction for “Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates,” by Yizhou Dong, Kevin T. Love, J. Robert Dorkin, Sasilada Sirirungruang, Yunlong Zhang, Delai Chen, Roman L. Bogorad, Hao Yin, Yi Chen, Arturo J. Vegas, Christopher A. Alabi, Gaurav Sahay, Karsten T. Olejnik, Weiheng...
Source: Proceedings of the National Academy of Sciences - April 15, 2014 Category: Science Tags: Corrections Source Type: research

Synthetic microRNAs can control infection Microbiology
Systematic genetic perturbation screening in human cells remains technically challenging. Typically, large libraries of chemically synthesized siRNA oligonucleotides are used, each designed to degrade a specific cellular mRNA via the RNA interference (RNAi) mechanism. Here, we report on data from three genome-wide siRNA screens, conducted to uncover host factors required...
Source: Proceedings of the National Academy of Sciences - March 25, 2014 Category: Science Authors: Franceschini, A., Meier, R., Casanova, A., Kreibich, S., Daga, N., Andritschke, D., Dilling, S., Ramo, P., Emmenlauer, M., Kaufmann, A., Conde–Alvarez, R., Low, S. H., Pelkmans, L., Helenius, A., Hardt, W.–D., Dehio, C., von Mering, C. Tags: Biological Sciences Source Type: research

Speeding evolution Engineering
As medicines become increasingly complex, their delivery becomes more challenging. To function, medicines must effectively navigate the body and reach their site of action. When the impediments to their delivery become too great, drug delivery vehicles are used. Small interfering RNA (siRNA) is a complex class of medicine. These duplex...
Source: Proceedings of the National Academy of Sciences - March 18, 2014 Category: Science Authors: Putnam, D. Tags: Commentaries Source Type: research

Lipopeptides and selective siRNA delivery Engineering
siRNA therapeutics have promise for the treatment of a wide range of genetic disorders. Motivated by lipoproteins, we report lipopeptide nanoparticles as potent and selective siRNA carriers with a wide therapeutic index. Lead material cKK-E12 showed potent silencing effects in mice (ED50 ∼ 0.002 mg/kg), rats (ED50
Source: Proceedings of the National Academy of Sciences - March 18, 2014 Category: Science Authors: Dong, Y., Love, K. T., Dorkin, J. R., Sirirungruang, S., Zhang, Y., Chen, D., Bogorad, R. L., Yin, H., Chen, Y., Vegas, A. J., Alabi, C. A., Sahay, G., Olejnik, K. T., Wang, W., Schroeder, A., Lytton-Jean, A. K. R., Siegwart, D. J., Akinc, A., Barnes, C., Tags: Physical Sciences Source Type: research

Inheritance of Trans Chromosomal Methylation Plant Biology
Hybridization in plants leads to transinteractions between the parental genomes and epigenomes that can result in changes to both 24 nt siRNA and cytosine methylation (mC) levels in the hybrid. In Arabidopsis the principle processes altering the hybrid methylome are Trans Chromosomal Methylation (TCM) and Trans Chromosomal deMethylation (TCdM) in...
Source: Proceedings of the National Academy of Sciences - February 4, 2014 Category: Science Authors: Greaves, I. K., Groszmann, M., Wang, A., Peacock, W. J., Dennis, E. S. Tags: Biological Sciences Source Type: research

Radiation killing is regulated by LGP2 Medical Sciences
An siRNA screen targeting 89 IFN stimulated genes in 14 different cancer cell lines pointed to the RIG-I (retinoic acid inducible gene I)–like receptor Laboratory of Genetics and Physiology 2 (LGP2) as playing a key role in conferring tumor cell survival following cytotoxic stress induced by ionizing radiation (IR). Studies...
Source: Proceedings of the National Academy of Sciences - January 28, 2014 Category: Science Authors: Widau, R. C., Parekh, A. D., Ranck, M. C., Golden, D. W., Kumar, K. A., Sood, R. F., Pitroda, S. P., Liao, Z., Huang, X., Darga, T. E., Xu, D., Huang, L., Andrade, J., Roizman, B., Weichselbaum, R. R., Khodarev, N. N. Tags: PNAS Plus Source Type: research

Consequences of HSV-1-induced AS1 deficiency Microbiology
Herpes simplex virus 1 (HSV-1) infection triggers specific metabolic changes in its host cell. To explore the interactions between cellular metabolism and HSV-1 infection, we performed an siRNA screen of cellular metabolic genes, measuring their effect on viral replication. The screen identified multiple enzymes predicted to influence HSV-1 replication, including...
Source: Proceedings of the National Academy of Sciences - December 17, 2013 Category: Science Authors: Grady, S. L., Purdy, J. G., Rabinowitz, J. D., Shenk, T. Tags: PNAS Plus Source Type: research

Codelivery of siRNA and a cisplatin prodrug Engineering
Cisplatin and other DNA-damaging chemotherapeutics are widely used to treat a broad spectrum of malignancies. However, their application is limited by both intrinsic and acquired chemoresistance. Most mutations that result from DNA damage are the consequence of error-prone translesion DNA synthesis, which could be responsible for the acquired resistance against...
Source: Proceedings of the National Academy of Sciences - November 12, 2013 Category: Science Authors: Xu, X., Xie, K., Zhang, X.-Q., Pridgen, E. M., Park, G. Y., Cui, D. S., Shi, J., Wu, J., Kantoff, P. W., Lippard, S. J., Langer, R., Walker, G. C., Farokhzad, O. C. Tags: Biological Sciences Source Type: research

MAPKAPK2 impairs replication of damaged DNA Cell Biology
DNA damage can obstruct replication forks, resulting in replicative stress. By siRNA screening, we identified kinases involved in the accumulation of phosphohistone 2AX (γH2AX) upon UV irradiation-induced replication stress. Surprisingly, the strongest reduction of phosphohistone 2AX followed knockdown of the MAP kinase-activated protein kinase 2 (MK2), a kinase currently implicated...
Source: Proceedings of the National Academy of Sciences - October 15, 2013 Category: Science Authors: Kopper, F., Bierwirth, C., Schon, M., Kunze, M., Elvers, I., Kranz, D., Saini, P., Menon, M. B., Walter, D., Sorensen, C. S., Gaestel, M., Helleday, T., Schon, M. P., Dobbelstein, M. Tags: Biological Sciences Source Type: research