Clinical OMICS

NOV-DEC 2017

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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4 Clinical OMICs November/December 2017 News siently or even chronically change the sequence of expressed, risk-modifying G to A variants, in order to lower a patient's risk of entering a disease state. "For instance, REPAIR could be used to functionally mimic A to G alleles of IFIH1 that protect against autoim- mune disorders such as type I dia- betes, immunoglobulin A deficiency, psoriasis, and systemic lupus erythe- matosus," the investigators added. Zhang and colleagues assayed a subset of the family of Cas13 enzymes for RNA knockdown activity in mammalian cells, identifying the Cas13b ortholog from Prevotella sp. P5-125 (PspCas13b) as the most effi- cient and specific for mammalian cell applications. Additional Disease- Modifying Potential Cas13b possesses pre-CRISPR RNA (crRNA) processing activity, allowing for multiplex editing of multiple vari- ants. Any one of these alone may not affect disease, but together might have additive effects and disease-modify- ing potential, the researchers said. "Extension of our rational design approach, such as combining promis- ing mutations and directed evolution, could further increase the specificity and efficiency of the system, while unbiased screening approaches could identify additional residues for improving REPAIR activity and speci- ficity," the investigators added. To demonstrate the first version of REPAIR (REPAIRv1), the research- ers tested the platform's ability to correct two disease mutations: 878G>A (AVPR2 W293X) in X-linked Nephrogenic diabetes insipidus, and 1517G>A (FANCC W506X) in Fanconi anemia—achieving 35% correction of AVPR2 and 23% correction of FANCC. Next, the researchers tested the ability of REPAIRv1 to correct 34 different disease-relevant G>A mutations, and were able to achieve significant edit- ing at 33 sites with up to 28% editing efficiency. An engineered variation of REPAIR (REPAIRv2) was used by the investi- gators to modify full-length stretches of RNA sequences containing known mutations. REPAIRv2 showed a greater than 919-fold increase in specificity. "The efficiency and specificity all seem promising as therapeutic tools but these need to be further evaluated in more cell types for efficiency and specificity," Qi said. "The expanded toolkits for RNA editing is opening up doors to study RNA biology and understand their significance in var- ious diseases. It may also become common tools for treating disease on a different layer in addition to DNA editing. He added: "Now, the Swiss Army Knife of CRISPR toolkit is further expanded and enriched." (continued from previous page) App Aids Research on How Genetic Risk Influences Heart Health Decisions Scientists at the Scripps Translational Sci- ence Institute and The Scripps Research Institute recently launched a smart- phone-app research study that seeks to understand how receiving personal genetic risk information impacts heart health decisions. Many health conditions, including coro- nary artery disease (CAD), are caused by a combination of our environment, behav- iors and genes. While patients can con- trol some factors that may impact their chances of developing disease, the contri- bution of their genes remains encoded in their DNA throughout their lives. The MyGeneRank app will provide users that have genetic data from 23andMe to obtain an estimated genetic risk score for coronary artery disease. The study will employ surveys and Apple HealthKit to determine if this information influences decision-making related to lifestyle modi- fication, and use of statin medications. "We want to determine whether or not knowledge of genetic risk impacts deci- sion-making when it comes to health behaviors or statin therapy," Ali Torka- mani, Ph.dD., director of genomics at the Scripps Translational Science Institute, and associate professor of integrative structural and computational biology at The Scripps Research Institute. "Using ResearchKit, we can reach more partici- pants via iPhone, expanding this study far beyond geographic barriers." emiliozv / Getty Images Sponk / Wikimedia Commons

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