Chliposome IFN-gamma-pDNA Naoparticle Therapy for Asthma

描述(申请人提供)：为了开发更好的治疗过敏性疾病的方法，包括哮喘和过敏性鼻炎，我们的目标是检查脂质体干扰素(基因纳米粒(CLIN)疗法的有效性和安全性。这一建议是基于哮喘基因治疗潜在应用的两个主要进展：(I)脂质体纳米粒与编码干扰素(CIN)的质粒经鼻腔注射(I.N.)通过将基因转移到肺中，可在哮喘小鼠肺中诱导显著的治疗效果，而不会产生实质性的干扰素-(Ii)由脂质体和脂质体(别名：chliposome，CLIN)组成的混合纳米颗粒可以提高肺内基因转移的效率。我们的工作假设是I.N.临床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疗法在吸入性过敏小鼠模型中是否有效，多大剂量的CLIN有效地提供保护，以及CLIN疗法是否将在慢性过敏性哮喘小鼠模型中提供保护。在第二个目标中，我们将评估CLIN疗法的安全性，我们计划评估有效剂量是否产生容易测量的不良反应。我们计划在给药后6、12、18和24小时监测炎症细胞因子和趋化因子以及急性时相蛋白在鼻和肺中的表达。可行性研究将解决的具体问题是：a)CLIN给药是否会引起急性局部或全身炎症反应，以及它是否会引起任何显著的毒性作用。该项目将由一群在过敏性疾病领域经验丰富的研究人员进行。拟议的研究结果有望促进我们对哮喘发病机制的了解，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.