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Combination of Genetics and Nanotechnology for Down Syndrome Modification: A Potential Hypothesis and Review of the Literature

机译:遗传和纳米技术相结合的唐氏综合症修改:一个潜在的假设和文献综述。

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摘要

Down syndrome (DS) is one of the most prevalent genetic disorders in humans. The use of new approaches in genetic engineering and nanotechnology methods in combination with natural cellular phenomenon can modify the disease in affected people. We consider two CRISPR/Cas9 systems to cut a specific region from short arm of the chromosome 21 (Chr21) and replace it with a novel designed DNA construct, containing the essential genes in chromatin remodeling for inactivating of an extra Chr21. This requires mimicking of the natural cellular pattern for inactivation of the extra X chromosome in females. By means of controlled dosage of an appropriate Nano-carrier (a surface engineered Poly D, L-lactide-co-glycolide (PLGA) for integrating the relevant construct in Trisomy21 brain cell culture media and then in DS mouse model, we would be able to evaluate the modification and the reduction of the active extra Chr21 and in turn reduce substantial adverse effects of the disease, like intellectual disabilities. The hypothesis and study seek new insights in Down syndrome modification.
机译:唐氏综合症(DS)是人类中最普遍的遗传性疾病之一。在基因工程和纳米技术中结合自然细胞现象使用新方法可以改变受影响人群的疾病。我们考虑使用两个CRISPR / Cas9系统从21号染色体的短臂(Chr21)切下特定区域,并用新颖设计的DNA构建体替换,该结构包含染色质重塑中的必需基因,以使多余的Chr21失活。这需要模仿自然细胞模式以使女性多余的X染色体失活。通过控制剂量的适当纳米载体(一种表面工程化的聚D,L-丙交酯-乙交酯),将相关构建体整合到Trisomy21脑细胞培养基中,然后整合到DS小鼠模型中,该假说和研究旨在评估唐氏综合症修饰的新见解,从而评估活性多余Chr21的修饰和减少,进而减少该疾病的大量不良反应,例如智力障碍。

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