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Molecular Dynamic Simulations of CRISPR and HIV

Abstract

In the United States, there were 37,600 new HIV infections in 2014, with an estimated 1.1 million people living with the disease in 2015, according to the CDC. HIV targets the cell receptor CD4 and chemocine coreceptors CCR5 or CXCR5. Some individuals possess a mutation within CCR5 that causes a resistance to HIV-1. One HIV+ patient in Berlin, Timothy Brown, developed an immunity to the virus after a bone marrow transplant from a donor who possessed this CCR5 mutation. After this coincidence, researchers attempted a variety of gene therapies, such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and Cas9. CRISPR/Cas9 is a promising new tool that scientists have been using to do direct editing of genomes with more ease and specificity than ever before. CRISPR stands for cluster of regularly interspaced palindromic repeats, which are segments of RNA that are found in many prokaryotes to defend the organism against viral infections and unwanted gene transfers. Cas is a gene cluster that mediates the response to the RNA encoded in the CRISPR segments. Cas are designated by the protein complex responsible for interference. Together, these molecules identify a segment of target RNA, extract it, and replace it with another segment. They make up part of the adaptive immune system of eukaryotic cells. This research hopes to create a predictive model by analyzing the existing gene therapy data from previous studies, and using numerical molecular dynamic simulation software to glean more information about those results. Previously published studies discuss how gene therapies such as ZFN and CRISPR are used to modify either the host genome or the viral genome3, and then experiments are performed to determine whether this therapy is effective at preventing viral infection. By analyzing the bonding characteristics of different strands of RNA, it may be possible to predict which RNA segments make the best candidates for gene therapies that will confer resistance to HIV infection

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