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Correction for Yan et al., Suppression of NF-{kappa}B activity via nanoparticle-based siRNA delivery alters early cartilage responses to inȷury Correction
MEDICAL SCIENCES Correction for “Suppression of NF-κB activity via nanoparticle-based siRNA delivery alters early cartilage responses to injury,” by Huimin Yan, Xin Duan, Hua Pan, Nilsson Holguin, Muhammad Farooq Rai, Antonina Akk, Luke E. Springer, Samuel A. Wickline, Linda J. Sandell, and Christine T. N. Pham, which appeared in issue...
Source: Proceedings of the National Academy of Sciences - May 9, 2017 Category: Science Tags: Corrections Source Type: research

Deubiquitinase YOD1 potentiates YAP/TAZ activities through enhancing ITCH stability Cell Biology
Hippo signaling controls the expression of genes regulating cell proliferation and survival and organ size. The regulation of core components in the Hippo pathway by phosphorylation has been extensively investigated, but the roles of ubiquitination−deubiquitination processes are largely unknown. To identify deubiquitinase(s) that regulates Hippo signaling, we performed unbiased siRNA...
Source: Proceedings of the National Academy of Sciences - May 1, 2017 Category: Science Authors: Youngeun Kim, Wantae Kim, Yonghee Song, Jeong-Rae Kim, Kyungjoo Cho, Hyuk Moon, Simon Weonsang Ro, Eunjeong Seo, Yeon-Mi Ryu, Seung-Jae Myung, Eek-Hoon Jho Tags: Biological Sciences Source Type: research

Phosphate-binding pocket in Dicer-2 PAZ domain for high-fidelity siRNA production Biochemistry
The enzyme Dicer produces small silencing RNAs such as micro-RNAs (miRNAs) and small interfering RNAs (siRNAs). In Drosophila, Dicer-1 produces ∼22–24-nt miRNAs from pre-miRNAs, whereas Dicer-2 makes 21-nt siRNAs from long double-stranded RNAs (dsRNAs). How Dicer-2 precisely makes 21-nt siRNAs with a remarkably high fidelity is unknown. Here we report...
Source: Proceedings of the National Academy of Sciences - December 5, 2016 Category: Science Authors: Suresh K. Kandasamy, Ryuya Fukunaga Tags: Biological Sciences Source Type: research

FoxO6 affects Plxna4-mediated neuronal migration during mouse cortical development Neuroscience
The forkhead transcription factor FoxO6 is prominently expressed during development of the murine neocortex. However, its function in cortical development is as yet unknown. We now demonstrate that cortical development is altered in FoxO6+/− and FoxO6−/− mice, showing migrating neurons halted in the intermediate zone. Using a FoxO6-directed siRNA approach,...
Source: Proceedings of the National Academy of Sciences - November 7, 2016 Category: Science Authors: Ricardo H. Paap, Saskia Oosterbroek, Cindy M. R. J. Wagemans, Lars von Oerthel, Raymond D. Schellevis, Annemarie J. A. Vastenhouw-van der Linden, Marian J. A. Groot Koerkamp, Marco F. M. Hoekman, Marten P. Smidt Tags: PNAS Plus Source Type: research

FoxO6 is essential in cortical development Neuroscience
The forkhead transcription factor FoxO6 is prominently expressed during development of the murine neocortex. However, its function in cortical development is as yet unknown. We now demonstrate that cortical development is altered in FoxO6+/− and FoxO6−/− mice, showing migrating neurons halted in the intermediate zone. Using a FoxO6-directed siRNA approach,...
Source: Proceedings of the National Academy of Sciences - November 7, 2016 Category: Science Authors: Paap, R. H., Oosterbroek, S., Wagemans, C. M. R. J., von Oerthel, L., Schellevis, R. D., Vastenhouw-van der Linden, A. J. A., Groot Koerkamp, M. J. A., Hoekman, M. F. M., Smidt, M. P. Tags: PNAS Plus Source Type: research

Nanoparticle injections show promise as treatment for osteoarthritis
This study is interesting, as it showed that these nanoparticles could reduce inflammation caused by joint injuries in mice. It's not yet clear from the study whether these nanoparticles will be effective once osteoarthritis has developed in the joint, so we would be interested to learn more and see how the research progresses."
Source: Arthritis Research UK - October 2, 2016 Category: Rheumatology Source Type: news

Selective NP delivery to cancer over normal cells Engineering
Conventional chemotherapeutics nonselectively kill all rapidly dividing cells, which produces numerous side effects. To address this challenge, we report the discovery of functional polyesters that are capable of delivering siRNA drugs selectively to lung cancer cells and not to normal lung cells. Selective polyplex nanoparticles (NPs) were identified by high-throughput...
Source: Proceedings of the National Academy of Sciences - September 26, 2016 Category: Science Authors: Yan, Y., Liu, L., Xiong, H., Miller, J. B., Zhou, K., Kos, P., Huffman, K. E., Elkassih, S., Norman, J. W., Carstens, R., Kim, J., Minna, J. D., Siegwart, D. J. Tags: PNAS Plus Source Type: research

Drosophila antiviral response Microbiology
Since its discovery, RNA interference has been identified as involved in many different cellular processes, and as a natural antiviral response in plants, nematodes, and insects. In insects, the small interfering RNA (siRNA) pathway is the major antiviral response. In recent years, the Piwi-interacting RNA (piRNA) pathway also has been...
Source: Proceedings of the National Academy of Sciences - July 18, 2016 Category: Science Authors: Petit, M., Mongelli, V., Frangeul, L., Blanc, H., Jiggins, F., Saleh, M.-C. Tags: PNAS Plus Source Type: research

NIR nanoparticles for imaging and siRNA delivery Medical Sciences
Anaplastic thyroid cancer (ATC), one of the most aggressive solid tumors, is characterized by rapid tumor growth and severe metastasis to other organs. Owing to the lack of effective treatment options, ATC has a mortality rate of ∼100% and median survival of less than 5 months. RNAi nanotechnology represents a...
Source: Proceedings of the National Academy of Sciences - July 11, 2016 Category: Science Authors: Liu, Y., Gunda, V., Zhu, X., Xu, X., Wu, J., Askhatova, D., Farokhzad, O. C., Parangi, S., Shi, J. Tags: Physical Sciences Source Type: research

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