Chliposome IFN-gamma-pDNA Naoparticle Therapy for Asthma

描述（由申请人提供）：为了开发更好的治疗过敏性疾病（包括哮喘和过敏性鼻炎）的方法，我们的目标是检查chliposome IFN-β基因纳米颗粒（CLIN）疗法的疗效和安全性。该提议基于哮喘基因治疗的潜在用途中的两个主要发展：（i）当鼻内（i. n.）递送至肺，在哮喘小鼠肺中诱导显著的治疗效果而不产生大量IFN-β，和（ii）肺中基因转移的功效可以用包含chliposome和脂质体（别名：chliposome，CLIN）的混合纳米颗粒增加。我们的工作假设是，CLIN治疗是一种安全有效的哮喘预防或治疗方法。本研究项目的具体目标如下。在第一个目标中，我们将评估CLIN疗法在吸入性过敏的小鼠模型中是否有效，CLIN有效提供保护的剂量以及CLIN疗法是否将在慢性过敏性哮喘的小鼠模型中提供保护。在第二个目标中，我们将评估放射治疗的安全性，我们计划评估有效剂量是否会产生可以容易测量的不良反应。我们计划在给药后6、12、18和24 h监测鼻和肺中炎性细胞因子和趋化因子以及急性期蛋白的表达。可行性研究将解决的具体问题是：a）CLIN给药是否诱导急性局部或全身炎症反应，以及是否诱导任何显著的毒性作用。该项目将由一组在过敏性疾病领域有经验的研究者进行。这项研究的结果有望提高我们对哮喘机制的认识，并可能导致开发预防和/或治疗哮喘的有效方法。

DESCRIPTION (provided by applicant): In an effort to develop a better treatment for allergic diseases, including asthma and allergic rhinitis, our goal is to examine the efficacy and safety of chliposome IFN-( gene nanoparticle (CLIN) Therapy. This proposal is based on the two major developments in potential use of gene therapy for asthma: (i) chliposome nanoparticles complexed with a plasmid encoding IFN-( (CIN) when intranasally (i.n.) delivered to the lung, induces significant therapeutic effects in the asthmatic mouse lung without producing substantial IFN-(, and (ii) the efficacy of gene transfer in the lung can be increased with hybrid nanoparticles, comprising chliposome and liposomes (alias: chliposomes, CLIN). Our working hypothesis is that i.n. CLIN therapy is a safe and effective prophylaxis or treatment for asthma. The specific aims of this research project are as follows. In the first aim, we will evaluate to evaluate whether CLIN therapy is effective in a mouse model of inhalant allergy, what dose of CLIN effectively provides protection and whether CLIN therapy will provide protection in a mouse model of chronic allergic asthma. In the second aim, we will evaluate the safety of CLIN-therapy, we plan to assess whether the effective dose produces unwanted adverse effects that can be readily measured. We plan to monitor the expression of inflammatory cytokines and chemokines and acute phase proteins in the nose and lung at 6, 12, 18 and 24 h after administration. The specific questions that the feasibility study will address are: a) whether CLIN administration induces acute local or systemic inflammatory responses and whether it induces any notable toxic effects. The project will be conducted by a group of investigators experienced in the field of allergic disease. The results of the proposed research are expected to advance our knowledge of the mechanisms of asthma and may lead to the development of an effective approach for the prevention and/or treatment of asthma.