Targeted Delivery of RNAi to Nerve Cells

RNAi 靶向递送至神经细胞

基本信息

批准号：
7404204
负责人：
ANTHONY A Ferrante
金额：
$ 14.97万
依托单位：
PHYSICAL SCIENCES, INC
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-01-15 至 2009-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7404204
关键词：
Address Adult Affect Animal Model Antibodies Biological Assay Brain Injuries Carrier Proteins Cell Line Cells Cessation of life Chemistry Chimeric Proteins Contracts Cytolysis Cytoplasm Development Diphtheria Toxin Disease Disease Progression Disulfide Linkage Dopamine Dose Evaluation Exhibits Gel Goals Government Green Fluorescent Proteins In Vitro Label Life Messenger RNA Methods Monitor Movement Muscle Rigidity Neuraxis Neurodegenerative Disorders Neurons Parkinson Disease Patients Persons Phase Phase I Clinical Trials Population Posture Process Production Protein Overexpression Proteins Public Health Purpose RNA Interference RNA Sequences Range Reporting Research Rest Tremor Signal Transduction Small Interfering RNA Substantia nigra structure Symptoms System Technology Tetanus Toxin Therapeutic Toxin Conjugates Transmembrane Domain Western Blotting desire dopaminergic neuron fluorescence microscope immunogenicity improved in vivo mRNA Transcript Degradation mutant novel pars compacta physical science protein aggregation synuclein targeted delivery uptake

项目摘要

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.

描述（由申请人提供）：帕金森氏病是一种常见的进行性神经退行性疾病，影响了成年人群的2％。在黑质中，多巴胺产生神经元的丧失导致静止震颤，缓慢运动，僵化和不稳定的姿势等症状。已经提出多巴胺能神经元的死亡是由于蛋白1-核蛋白的聚集。为了改善治疗治疗方案，需要改善对神经元细胞的靶向递送系统。物理科学公司（PSI）提议将靶向的小型干扰RNA（siRNA）与1-突触核蛋白蛋白与载体分子相结合，以特异性地递送至神经元。第二阶段的工作将开发一种有效的方法来大规模生产siRNA结合物，并将评估活动物模型中最有效的体内递送模式。我们预计拟议的系统将提供足够的siRNA，以将1-核蛋白的产量减少至少80％。帕金森氏病患者可以使用有限的治疗选择。 1-核蛋白已被认为是帕金森氏病有害作用的病因。在拟议的研究期间开发的技术将减少神经细胞中1-核蛋白的产生，因此应减缓疾病的进展。