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siRNA Screening: Development of Hit Stratification Strategies
Žaklina Strezoska, Annaleen Vermeulen, Emily M. Anderson, Anja Smith, Devin Leake

This poster compares different approaches to hit stratification and validation after an initial screen. Standard siRNA reagents deconvoluted from a pooled set of four were compared to a pooled set of four specificity enhanced reagents. High confidence hits were similar. To explore the validity of low confidence hits, a chimeric approach was used whereby a gene-specific seed sequence was introduced into a non-targeting siRNA scaffold. This work resulted in new hit stratification strategies.

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The Chemical Synthesis of Long and Highly Modified RNA using 2'-ACE Chemistry
Xiaoqin Cheng, Kristina Larson, Letitia Kwok, David Mierzejewski, Shawn Begay, Randy Rauen, Kelly Grimsley, Kaizhang He, Michael Delaney, David Kitchen, Amanda Haas, Melissa Kelley, Anja van Brabant Smith

Dharmacon has previously developed a novel RNA synthesis chemistry making RNA synthesis as reliable, accessible and of comparable quality as routinely observed in DNA synthesis.

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Specificity of highly potent miRNA inhibitors
Barbara Robertson, Andrew Dalby, Yuriy Fedorov, Jon Karpilow, Anastasia Khvorova1, Devin Leake, Annaleen Vermeulen

miRNA inhibitors are invaluable tools for elucidating the roles of miRNAs. However, potent inhibitors may also affect other miRNAs. To understand the potential cross-reactivity of miRNA inhibitors, various miRNA inhibitor designs were systematically tested. We demonstrate that mismatches both within and outside the seed region of the miRNA interfere with inhibition. Our findings indicate that features important for natural miRNA target recognition are also important for inhibitor specificity.

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Targeting Cancer Stem Cell-Related miRNAs for Prostate Cancer Therapy
ANSHIKA NIKITA SINGH, MEGHNA BARUAH, NEETI SHARMA

The poster focuses on the pivotal function of miRNAs in tumorigenesis by regulation of self renewal and apoptosis via cancer stem cell signalling pathways with special focus on their regulation of Epithelial to Mesenchymal transition in metastatic prostate cancer.

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siRNA Screening: Development of Hit Stratification Strategies
Žaklina Strezoska, Annaleen Vermeulen, Emily M. Anderson, Anja Smith, Devin Leake

This poster compares different approaches to hit stratification and validation after an initial screen. Standard siRNA reagents deconvoluted from a pooled set of four were compared to a pooled set of four specificity enhanced reagents. High confidence hits were similar. To explore the validity of low confidence hits, a chimeric approach was used whereby a gene-specific seed sequence was introduced into a non-targeting siRNA scaffold. This work resulted in new hit stratification strategies.

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Identification of microRNA targets using microRNA modulation techniques and gene expression arrays
Emily M. Anderson, Maren Mayer, Kevin Sullivan, Barbara Robertson, Žaklina Strezoska, Annaleen Vermeulen, and Devin Leake

By examining the overlap of messages down-regulated by miRNA mimics and up-regulated by miRNA inhibitors, we robustly identify miRNA-regulated messages, many of which have canonical seed matches and some which are not identied by standard target prediction programs.

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Specificity and functionality of microRNA inhibitors
Barbara Robertson, Andrew Dalby, Jon Karpilow, Anastasia Khvorova, Devin Leake and Annaleen Vermeulen

Our findings indicate that features important for natural miRNA target recognition also appear to be important for inhibitor specificity. Understanding the specificity of inhibitors allows for better interpretation of inhibitor activity in endogenous systems.

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Alternative miRNA design for therapeutic RNAi applications
Anja van Brabant Smith, Barb Robertson, Annaleen Vermeulen, Christina Yamada, Angela Reynolds, Anastasia Khvorova, Devin Leake

For in vivo applications, the design of miRNA inhibitors and miRNA mimics must be optimized for stability and potency. However, stabilized miRNA mimic molecules can lose functionality compared to standard miRNA mimic molecules due, in part, to the activity of the stabilized passenger strand acting as a miRNA inhibitor. We discuss how mismatches affect the activity of the stabilized miRNA mimics, perhaps by generating a passenger strand that is less functional as an inhibitor molecule.

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Safety Of A Sublingual Tablet of House Dust Mite Allergen Extracts In An Environmental Exposure Chamber Study
Michel Roux, Agnès Viatte, Robert K. Zeldin

In an environmental exposure chamber (EEC) study, treatment with HDM sublingual tablets in patients with HDM-associated allergic rhinitis was generally well tolerated regardless of dose. While asthma and related symptoms were more common during the peri-EEC challenge periods, rates did not differ between active and placebo treatment.

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Scientific News
The Rise of 3D Cell Culture and in vitro Model Systems for Drug Discovery and Toxicology
An overview of the current technology and the challenges and benefits over 2D cell culture models plus some of the latest advances relating to human health research.
World’s Largest Coral Gene Database
‘Genetic toolkit’ will help shed light on which species survive climate change.
A Boost for Regenerative Medicine
Growing tissues and organs in the lab for transplantation into patients could become easier after scientists discovered an effective way to produce three-dimensional networks of blood vessels, vital for tissue survival yet a current stumbling block in regenerative medicine.
Breast Cancer Drug Hope
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Untangling Disease-Related Protein Misfolding
Work advances understanding of genetic forms of thrombosis, emphysema, cirrhosis of the liver, neurodegenerative diseases and inflammation, among others.
Early Genetic Changes in Premalignant Colorectal Tissue Identified
Findings point to drivers of early cancer development, targets for cancer prevention therapies.
Harnessing Nature’s Vast Array of Venoms for Drug Discovery
Scripps scientists have developed a method for rapidly identifying venoms.
Nanoparticles Target, Transform Fat Tissue
Nanoparticles designed to target white fat and convert it to calorie-burning brown fat slowed weight gain in obese mice without affecting food intake. This proof-of-concept work could lead to new therapies to treat obesity.
New Cancer Fighters Emerge From Lab
Rice University lab simplifies total synthesis of anti-cancer agent.
Scientists Find Evidence That Cancer Can Arise Changes
Researchers at Rockefeller University have found a mutation that affects the proteins that package DNA without changing the DNA itself can cause a rare form of cancer.
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