Targeted Delivery of RNAi to Nerve Cells

描述（由申请人提供）：帕金森病是一种常见的进行性神经退行性疾病，影响2%的成年人群。黑质神经元中产生多巴胺的神经元的损失导致诸如静止性震颤、缓慢运动、僵硬和姿势不稳定的症状。多巴胺能神经元的死亡被认为是由于蛋白质1-突触核蛋白的聚集。一种改进的神经元细胞靶向递送系统对于改善治疗选择是必要的。物理科学公司(PSI)提出将针对1-突触核蛋白的靶向小干扰RNA（siRNA）缀合至载体分子，用于特异性递送至神经元。第二阶段的努力将开发一种有效的方法，大规模生产的siRNA结合物，并将评估最有效的模式，在体内交付活动物模型。我们预计，所提出的系统将提供足够的siRNA，以减少至少80%的1-突触核蛋白的生产。帕金森病患者的治疗选择有限。1-已经提出突触核蛋白是帕金森病有害作用的病原体。在拟议的研究中开发的技术将减少神经细胞中1-突触核蛋白的产生，因此应该减缓疾病的进展。

DESCRIPTION (provided by applicant): Parkinson's disease is a common progressive neurodegenerative disorder that affects 2% of the adult population. The loss of dopamine producing neurons in the substantia nigra pars compacta results in such symptoms as a resting tremor, slow movement, rigidity and unstable posture. The death of the dopaminergic neurons has been proposed to be due to aggregation of the protein 1-synuclein. An improved targeted delivery system to neuronal cells is necessary to improve therapeutic treatment options. Physical Sciences Inc. (PSI) proposes to conjugate a targeted small interfering RNA (siRNA) against 1- synuclein protein to a carrier molecule for specific delivery to neurons. The Phase II effort will develop an effective method for large-scale production of the siRNA conjugate and will evaluate the most efficient mode of in vivo delivery in live animal models. We anticipate that the proposed system will deliver sufficient siRNA to reduce the production of 1-synuclein by at least 80%.Project Narrative Relevance to public health. Limited treatment options are available to patients with Parkinson's disease. 1-Synuclein has been proposed to be a causative agent of deleterious effects of Parkinson's disease. The technology developed during the proposed research will reduce the production of 1-synuclein in nerve cells and should therefore slow the progression of the disease.