84 research outputs found
Abstract LB-271: SplashRNA, a sequential classification algorithm for ultra-potent RNAi
No full textAbstract
We present SplashRNA, a sequential classifier - analogous to face detection algorithms - to predict ultra-potent microRNA-based short hairpin RNAs (shRNAs) for virtually any gene. Trained on existing and novel large-scale datasets, SplashRNA outperforms previous algorithms and reliably predicts the most efficient shRNAs for a given gene. Combined with the optimized miR-E backbone, >90% of high-scoring SplashRNA predictions trigger >85% protein knockdown when expressed from a single genomic integration. SplashRNA can significantly improve the accuracy of loss-of-function genetics studies and facilitates the generation of compact shRNA libraries. The open source SplashRNA platform completes the RNAi toolkit to harness microRNA-based shRNAs for robust single-gene and multiplexed inducible and reversible target inhibition.
Citation Format: Raphael Pelossof, Lauren Fairchild, Christina S. Leslie, Christof Fellmann. SplashRNA, a sequential classification algorithm for ultra-potent RNAi [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-271. doi:10.1158/1538-7445.AM2017-LB-271</jats:p
Abstract B37: RNAi and CRISPR/Cas9-based in vivo models for drug discovery
No full textAbstract
With the advent of RNAi and more recently CRISPR/Cas9 technologies, the speed and precision by which genetically engineered mouse models of cancer can be created is unprecedented. Having previously engineered a miRE scaffold for enhanced shRNA processing and now with the introduction of a powerful new SplashRNA algorithm for accurate shRNA prediction, we have brought RNAi technology to its peak by increasing potency and reducing off-target effects, such that it can be effectively exploited to preclinically mimic drug therapy and even combination therapy not only in vitro but also in live mice. Here, we take advantage of Cas9-expressing mice and demonstrate that in situ delivery of sgRNAs can lead to somatic mutagenesis to promote rapid tumorigenesis in mice. By combining this approach with inducible and reversible RNAi-mediated gene silencing to mimic drug therapy in the same mice, we now have an advanced platform to perform target validation and toxicity assessment of novel candidate targets in vivo. Here, we showcase how synergizing our RNAi and CRISPR/Cas9 genetic toolbox will help facilitate cancer drug discovery research and increase our confidence in predicting drug responses in humans into a new era.
Citation Format: Prem K. Premsrirut, Chia-Lin Wang, Yu-ting Yang, Rafii Pelossof, Christina Leslie, Christof Fellmann, Lukas Dow, Johannes Zuber, Scott Lowe. RNAi and CRISPR/Cas9-based in vivo models for drug discovery [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr B37.</jats:p
Aktuelles Wirtschaftsstrafrecht
No full textKein Abstract vorhanden.+ ID der Publikation: unilu_6833 + Sprache: Deutsch + Letzte Aktualisierung: 2018-10-05 10:26:4
Das Verbot von extremistischen Organisationen im schweizerischen Recht
No full textBans on organizations are not part of the traditional range of instruments used in dealing with extremist phenomena in the Swiss legal system. In recent years, however, there has been a paradigm shift in this regard, especially since there has been a general, abstract basis for a ban on extremist organizations in individual cases for the first time since September 1, 2017.
This thesis is devoted to the question of the conditions under which a ban on extremist organizations is permissible from a constitutional point of view. To this end, the author examines whether and to what extent extremist efforts enjoy protection under fundamental rights. He also examines the existing legal bases for bans on organisations, specifically Article 74 of the Intelligence Service Act (NDG), for their conformity with the constitution
Vico in una nuova chiave di lettura
No full textTraducción del inglés por Pablo Badillo O’FarrellEl Autor expone su interpretación de Vico y las circunstancias que, desde los años ’70, han rodeado sus
propuestas. A su vez, el Autor muestra resumidos en cinco los conceptos-clave que han guiado su investigación
viquiana desde 1970: primado de la fantasía; primitivismo cultural; religión; origen del lenguaje; y barbarie de la
reflexión.The author explains his interpretation of Vico and the critical circumstances that have surrounded his proposals
since the 1970s. In turn, the Author clearly shows the five key concepts that have guided his Viquian research
since 1970: primacy of fantasy; cultural primitivism; religion; origin of language; and barbarism of reflection.Nel presente contributo l’Autore espone la propria interpretazione di Vico e le circostanze che, a partire
dagli anni ’70, hanno orientato le sue proposte. Inoltre, l’Autore spiega i cinque concetti chiave che hanno guidato
la sua ricerca vichiana dal 1970: primato della fantasia, primitivismo culturale, religione, origine della lingua
e barbarie di riflessione
Supplementation of intrathecal bupivacaine with clonidine in ex-premature neonates [8] (multiple letters)
No full text[No abstract available]Bouchut JC, 2001, REGION ANESTH PAIN M, V26, P83; Breschan C, 1999, PAEDIATR ANAESTH, V9, P81, DOI 10.1046-j.1460-9592.1999.00277.x; Fellmann C, 2002, PAEDIATR ANAESTH, V12, P637, DOI 10.1046-j.1460-9592.2002.00924.x; Rochette A, 2004, ANESTH ANALG, V98, P56, DOI 10.1213-01.ANE.0000093229.17729.6C0
Cornerstones of CRISPR–Cas in drug discovery and therapy
No full textThe recent development of CRISPR-Cas systems as easily accessible and programmable tools for genome editing and regulation is spurring a revolution in biology. Paired with the rapid expansion of reference and personalized genomic sequence information, technologies based on CRISPR-Cas are enabling nearly unlimited genetic manipulation, even in previously difficult contexts, including human cells. Although much attention has focused on the potential of CRISPR-Cas to cure Mendelian diseases, the technology also holds promise to transform the development of therapies to treat complex heritable and somatic disorders. In this Review, we discuss how CRISPR-Cas can affect the next generation of drugs by accelerating the identification and validation of high-value targets, uncovering high-confidence biomarkers and developing differentiated breakthrough therapies. We focus on the promises, pitfalls and hurdles of this revolutionary gene-editing technology, discuss key aspects of different CRISPR-Cas screening platforms and offer our perspectives on the best practices in genome engineering
- …
