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VACCINATION BY TOPICAL APPLICATION OF CONDENSED DNA

通过局部应用浓缩 DNA 进行疫苗接种

基本信息

批准号：
6211596
负责人：
MARK J COOPER
金额：
$ 10万
依托单位：
COPERNICUS THERAPEUTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-09-30 至 2001-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6211596
关键词：
DNA active immunization gene targeting hepatitis B laboratory mouse luciferin monooxygenase nucleic acid sequence plasmids technology /technique development topical drug application transfection vaccine development vector vaccine virus antigen western blottings

项目摘要

Topically applied DNA vaccines may provide a safe, easy, needle-less, and cost-effective means of eliciting immunity, and has significant potential to improve world health. Recent data indicate that various skin cells can be transfected following a topical application of naked DNA. Specific immunity to DNA-encoded antigens has been observed, although the immune response following cutaneous administration has been less robust than either IM vaccination protocols or recombinant protein vaccines. Hence, commercialization of this technology is limited by technical constraints in gene transfer efficiency. Copernicus Therapeutics has developed a non-viral gene delivery technology that compacts single plasmid DNA molecules into 20-25 nm particles, termed PLASmin(TM) complexes. Our formulation is simple and reproducible, and PLASmin(TM) complexes readily transfect non-dividing, post-mitotic human cells. Our formulations are stable in normal saline and serum, and highly resistant to nuclease digestion. PLASmin(TM) complexes are stable for months and can be concentrated to approximately 7 mg/ml without loss of stability or integrity. To determine if PLASmin(TM) complexes can improve gene transfer results, several formulations will be applied to murine skin, and antibody responses to encoded antigens will be assessed. If successful, optimized PLASmin(TM) complexes will be used in a Phase II SBIR application to vaccinate humans against hepatitis. PROPOSED COMMERCIAL APPLICATION: Although naked DNA applied to skin has the potential to elicit an immune response, limitations in gene expression may hinder commercial development. Copernicus has developed a novel, non-viral technology in which single molecules of DNA are condensed with polycationic proteins. This formulation greatly improves gene transfer results in vitro and in preclinical models. If our formulation can elicit robust immunity in mice following topical application, then this DNA vaccine platform could be used to develop many products for infectious disease and cancer indications.

局部应用的DNA疫苗可以提供一种安全、简便、无针且具有成本效益的引发免疫的手段，并且具有改善世界健康的巨大潜力。最近的数据表明，各种皮肤细胞可以转染后，局部应用裸DNA。已经观察到对DNA编码的抗原的特异性免疫，尽管皮肤施用后的免疫应答不如IM疫苗接种方案或重组蛋白疫苗稳健。因此，该技术的商业化受到基因转移效率的技术限制。Copernicus Therapeutics开发了一种非病毒基因传递技术，该技术将单个质粒DNA分子压缩成20-25 nm的颗粒，称为PLASmin（TM）复合物。我们的配方简单且可重复，PLASmin（TM）复合物易于抑制非分裂的有丝分裂后的人类细胞。我们的制剂在生理盐水和血清中稳定，对核酸酶消化具有高度抗性。PLASmin（TM）复合物可稳定数月，并可浓缩至约7 mg/ml而不损失稳定性或完整性。为了确定PLASmin（TM）复合物是否可以改善基因转移结果，将几种制剂应用于小鼠皮肤，并评估对编码抗原的抗体应答。如果成功，优化的PLASmin（TM）复合物将用于第二阶段SBIR应用，为人类接种肝炎疫苗。拟定商业应用：尽管将裸DNA应用于皮肤有可能引发免疫反应，但基因表达的限制可能会阻碍商业开发。哥白尼开发了一种新的非病毒技术，其中单分子DNA与聚阳离子蛋白质缩合。该制剂极大地改善了体外和临床前模型中的基因转移结果。如果我们的制剂在局部应用后可以在小鼠中引发强大的免疫力，那么这种DNA疫苗平台可以用于开发许多用于感染性疾病和癌症适应症的产品。