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Total 125 results found since Jan 2013.

Business Office Feature Webinar | CRISPR/Cas9 in drug discovery: Applications in target discovery, validation, and hit screening
The CRISPR/Cas9 system allows for unprecedented ease and control when editing the genome. Its potential impact on drug discovery is vast, including enabling gene and cell replacement therapies, identifying novel drug targets through functional genomic screens, and simplifying the production of disease models using permanent knockouts for validating therapy targets and testing drug efficacy. But in practical terms, how is CRISPR/Cas9 currently being applied, and where might the future challenges and pitfalls be? Furthermore, how do assays based on the new CRISPR/Cas9 technology compare with current screening methodologies, ...
Source: ScienceNOW - May 5, 2016 Category: Science Authors: Lorenz Mayr Tags: Science Webinar Series Source Type: news

RNAi-based nanomedicines for gene silencing Applied Biological Sciences
Despite progress in systemic small interfering RNA (siRNA) delivery to the liver and to solid tumors, systemic siRNA delivery to leukocytes remains challenging. The ability to silence gene expression in leukocytes has great potential for identifying drug targets and for RNAi-based therapy for leukocyte diseases. However, both normal and malignant...
Source: Proceedings of the National Academy of Sciences - January 5, 2016 Category: Science Authors: Weinstein, S., Toker, I. A., Emmanuel, R., Ramishetti, S., Hazan-Halevy, I., Rosenblum, D., Goldsmith, M., Abraham, A., Benjamini, O., Bairey, O., Raanani, P., Nagler, A., Lieberman, J., Peer, D. Tags: PNAS Plus Source Type: research

Production of functional siRNAs by human Dicer Microbiology
Although RNA interference (RNAi) functions as a potent antiviral innate-immune response in plants and invertebrates, mammalian somatic cells appear incapable of mounting an RNAi response and few, if any, small interfering RNAs (siRNAs) can be detected. To examine why siRNA production is inefficient, we have generated double-knockout human cells lacking...
Source: Proceedings of the National Academy of Sciences - December 15, 2015 Category: Science Authors: Kennedy, E. M., Whisnant, A. W., Kornepati, A. V. R., Marshall, J. B., Bogerd, H. P., Cullen, B. R. Tags: PNAS Plus Source Type: research

Enhancing potency of siRNA for fusion genes Applied Biological Sciences
Canonical siRNA design algorithms have become remarkably effective at predicting favorable binding regions within a target mRNA, but in some cases (e.g., a fusion junction site) region choice is restricted. In these instances, alternative approaches are necessary to obtain a highly potent silencing molecule. Here we focus on strategies for...
Source: Proceedings of the National Academy of Sciences - December 1, 2015 Category: Science Authors: Gavrilov, K., Seo, Y.-E., Tietjen, G. T., Cui, J., Cheng, C. J., Saltzman, W. M. Tags: PNAS Plus Source Type: research

Whole-genome siRNA screening for AAV permissivity Cell Biology
Viral vectors based on the adeno-associated virus (AAV) hold great promise for in vivo gene transfer; several unknowns, however, still limit the vectors’ broader and more efficient application. Here, we report the results of a high-throughput, whole-genome siRNA screening aimed at identifying cellular factors regulating AAV transduction. We identified 1,483...
Source: Proceedings of the National Academy of Sciences - September 8, 2015 Category: Science Authors: Mano, M., Ippodrino, R., Zentilin, L., Zacchigna, S., Giacca, M. Tags: Biological Sciences Source Type: research

PHB1 siRNA nanoparticles for cancer treatment Engineering
RNA interference (RNAi) represents a promising strategy for identification and validation of putative therapeutic targets and for treatment of a myriad of important human diseases including cancer. However, the effective systemic in vivo delivery of small interfering RNA (siRNA) to tumors remains a formidable challenge. Using a robust self-assembly strategy,...
Source: Proceedings of the National Academy of Sciences - June 23, 2015 Category: Science Authors: Zhu, X., Xu, Y., Solis, L. M., Tao, W., Wang, L., Behrens, C., Xu, X., Zhao, L., Liu, D., Wu, J., Zhang, N., Wistuba, I. I., Farokhzad, O. C., Zetter, B. R., Shi, J. Tags: Biological Sciences Source Type: research

Lack of pairing triggers multigenerational RNAe Genetics
Single-copy transgenes in Caenorhabditis elegans can be subjected to a potent, irreversible silencing process termed small RNA-induced epigenetic silencing (RNAe). RNAe is promoted by the Piwi Argonaute protein PRG-1 and associated Piwi-interacting RNAs (piRNAs), as well as by proteins that promote and respond to secondary small interfering RNA (siRNA) production....
Source: Proceedings of the National Academy of Sciences - May 19, 2015 Category: Science Authors: Leopold, L. E., Heestand, B. N., Seong, S., Shtessel, L., Ahmed, S. Tags: PNAS Plus Source Type: research

siRNA-toting nanoparticles inhibit breast cancer metastasis
Researchers combined finely crafted nanoparticles with one of nature's potent disrupters to prevent the spread of triple-negative breast cancer in mouse models. The researchers are working toward clinical trials and exploring use of the technology for other cancers and diseases.
Source: ScienceDaily Headlines - May 12, 2015 Category: Science Source Type: news

New Ebola treatment effective three days after infection
A post-exposure treatment that is effective against a specific strain of the Ebola virus that killed thousands of people in West Africa has been developed by researchers. The treatment uses a sequence specific short strand of RNA, known as siRNA, designed to target and interfere with the Ebola virus, rendering it harmless. One of the advantages of this approach is the ability to quickly modify it to different viral strains.
Source: ScienceDaily Headlines - April 22, 2015 Category: Science Source Type: news

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

Development of refractoriness of HO‐1 induction to a second treatment with UVA radiation and the involvement of Nrf2 in human skin fibroblasts
This study demonstrates that the levels of HO‐1 protein are also reduced after a second dose of UVA radiation as are Nrf2 levels, and there is less accumulation of Nrf2 in the nucleus where as Bach1 does accumulate in the nucleus. Cell viability is further reduced and cell membrane damage increased as compared with a single UVA treatment when an initial UVA treatment was followed by a second dose. Knockdown of Nrf2 by siRNA (siNrf2) targeting caused additional refractoriness of HO‐1 protein induction to a second UVA or heme treatment and this treatment also further enhanced cell damage by a second dose of UVA radiation...
Source: Photochemistry and Photobiology - September 11, 2014 Category: Science Authors: Julia Li Zhong, Chintan M. Raval, Muhammad Farrukh Nisar, ChunXiang Bian, Jin Zhang, Li Yang, Rex M. Tyrrell Tags: Research Article 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