PREVENTING TRANSMISSION OF DISEASES--AIDS VIA BLOOD

预防疾病传播——艾滋病通过血液传播

• 批准号: 3362110
• 负责人: JAMES L MATTHEWS
• 金额: $ 23.97万
• 依托单位: BAYLOR RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-15 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3362110
• 关键词: Macaca mulatta; Trypanosoma cruzi; animal tissue; antiviral agents; baboons; blood banks; blood preservation; blood transfusion; chemical synthesis; communicable disease control; communicable disease transmission; cytomegalovirus; dyes; human immunodeficiency virus; human tissue; lasers; natural gene amplification; nonvisual photosensitivity; photochemistry; provirus; radiosensitizer; simian AIDSs

The project objectives are to develop a photodynamic treatment to render blood bank products free from envelope viruses including cytomegalovirus (CMV) and human immunodeficiency virus (HIV) and to kill malarial organisms and trypanosomes known to be transmitted via transfusion. A means to treat blood is essential because semlogic tests cannot identify all infected blood. Preliminary research in our laboratory has shown photodynamic killing of enveloped viruses (CMV, ERV, and others), malaria, and T. cruzi in free suspension as well as in whole blood and HIV within infected H9 cells. Tbe photoactive compound dihematoporphyrin ether (DHE) was activated in a flowing system using 630 mn light at 5 J/cm2. Initial tests for effects of the system on blood quality were also done as the proposed system must kill infectious agents without modification of essential blood elements. To further develop this photoactive system with DHE, a simian immunodeficiency virus andffl model will be used for infectivity testing including detection of provirus in cells by the polymemse chain reaction. Human and baboon blood will be used for other tests including RBC life span, platelet function, and pmtein integrity. A scaled up prototype system allows blood to be processed in 500 ml units. Additional toxicity and mutagenicity studies of DHE will be done. Although the DHE system will be fully developed, other photoactive dyes will be investigated in an effort to increase the efficiency of the photokilling system. The present system limits the light power that can be delivered because hemoglobin also absorbs at 630 nin. Preliminary tests here on other dyes that absorb at 700 nm (minimal hemoglobin absorption) and are more efficient at low light levels indicate that othcr dyes are worthy of intensive investigation. Collaborative arrangements have been established between our organic synthesis laboratory and three other university laboratories to develop new candidate dyes for antiviral screening and development. If these dyes prove advantageous over the existing system, they will be fully tested in the aninial model. The most efficient new dyes will follow the DHE test protocol. Our goal is the development of an efficient system for the inactivation of viral pathogens in free suspension and within ceus that also kills malaria and T. cruzi . The system should retain the integrity of all blood components, process a unit of blood in less than 10 minutes, and be adaptable for blood banks.

该项目的目标是开发一种光动力处理方法来渲染 不含包膜病毒（包括巨细胞病毒）的血库产品 (CMV) 和人类免疫缺陷病毒 (HIV) 并杀死疟疾 已知通过输血传播的生物体和锥虫。一个 治疗血液的方法至关重要，因为符号学测试无法识别 所有被感染的血液。我们实验室的初步研究表明 光动力杀死包膜病毒（CMV、ERV 等）， 疟疾和克氏锥虫在游离悬浮液以及全血和 受感染的 H9 细胞内的 HIV。 Tbe光活性化合物二血卟啉 乙醚 (DHE) 在流动系统中使用 6.3 亿光在 5 ℃ 下被激活 焦耳/平方厘米。还进行了系统对血液质量影响的初步测试 这样做是因为拟议的系统必须杀死传染性病原体而无需 改变必需的血液元素。为了进一步发展这一 具有 DHE（一种猿猴免疫缺陷病毒）和ffl 模型的光活性系统 将用于感染性测试，包括检测原病毒 细胞通过聚合酶链式反应。人类和狒狒的血液将 用于其他测试，包括红细胞寿命、血小板功能和 蛋白质完整性。放大的原型系统允许血液 以 500 毫升为单位进行加工。额外的毒性和致突变性研究 DHE 将完成。虽然DHE系统将全面开发， 将研究其他光活性染料，以努力提高 光杀伤系统的效率。目前的制度限制了 由于血红蛋白也在 630 处吸收，因此可以传递光功率 九。这里对其他在 700 nm 处吸收的染料进行了初步测试（最小 血红蛋白吸收）并且在低光照水平下效率更高 表明其他染料值得深入研究。 我们的有机组织之间已经建立了合作安排 合成实验室和其他三个大学实验室正在开发 用于抗病毒筛选和开发的新候选染料。 如果这些 事实证明，染料比现有系统更有优势，它们将得到充分利用 在动物模型中进行了测试。最有效的新型染料将遵循 DHE 测试协议。我们的目标是开发一个高效的系统 游离悬浮液和细胞内病毒病原体的灭活 这也能杀死疟疾和克氏锥虫。系统应保留 所有血液成分的完整性，在不到 10分钟，即可适应血库。