Chliposome IFN-gamma-pDNA Naoparticle Therapy for Asthma

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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.