Display of HIV Binding Proteins on Bacterial S-Layers

细菌 S 层上 HIV 结合蛋白的展示

• 批准号: 6551173
• 负责人: DAVID A SIMPSON
• 金额: $ 13.52万
• 依托单位: OSEL, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6551173
• 关键词: AIDS education /prevention; Lactobacillus; binding proteins; biotherapeutic agent; communicable disease transmission; genetic manipulation; microorganism growth; recombinant DNA; recombinant proteins; surface antigens; vagina

DESCRIPTION (provided by applicant): Osel Inc. is striving to develop a novel approach to prevent vaginal HIV transmission. This approach involves genetically modifying non-pathogenic bacteria, resembling those found on mucosal surfaces, to produce molecules that have the capacity to bind, trap, and inactivate HIV. By colonizing the vaginal cavity with these bacteria, HIV will have the same affinity for the modified bacteria as the host cell. Binding of HIV to these modified bacteria should block subsequent transmission of virus to the host. As outlined in the present application, we propose to engineer a specific vaginally-derived strain of lactobacillus, L. crispatus, to express high affinity HIV binding proteins. Since L. crispatus is surrounded by a dense, proteinaceous surface component (S-layer), we propose to display a series of different HIV binding proteins on this S-layer, thus positioning these molecules to have ready access to HIV when introduced into the vaginal cavity. In these phase I studies, we will genetically modify these bacteria to display HIV binding ligands within various domains of the S-layer. We will subsequently demonstrate that these modified bacteria block HIV-infectivity in vitro. If completed successfully, these studies will position us to pursue in vivo testing of this product during Phase II investigations. PROPOSED COMMERCIAL APPLICATION: The novel approach proposed by Osel Inc. would find utility as a method to block HIV transmission. Since it is anticipated to be cost-effective, it can be used world-wide, including in under-developed countries. This product will be marketed as a vaginal suppository to be used on a weekly, or monthly, basis. It will be convenient to use and female-controlled. Importantly, this product concept is associated with an unmet medical meed and substantial commercial opportunity.

描述（由申请人提供）：Osel Inc. 正在努力开发一种预防阴道 HIV 传播的新方法。 这种方法涉及对非致病性细菌（类似于粘膜表面的细菌）进行基因改造，以产生能够结合、捕获和灭活艾滋病毒的分子。 通过在阴道腔内定植这些细菌，HIV 对修饰细菌的亲和力将与宿主细胞相同。 HIV 与这些经过修饰的细菌结合应该会阻止病毒随后传播给宿主。 如本申请中概述的，我们建议设计一种特定的阴道来源的乳杆菌菌株，卷曲乳杆菌，以表达高亲和力的HIV结合蛋白。 由于卷曲乳杆菌被致密的蛋白质表面成分（S 层）包围，我们建议在该 S 层上展示一系列不同的 HIV 结合蛋白，从而将这些分子定位为在引入到 HIV 中时可以随时接触 HIV。阴道腔。 在这些第一阶段研究中，我们将对这些细菌进行基因改造，使其在 S 层的各个域内展示 HIV 结合配体。 我们随后将证明这些经过修饰的细菌可以在体外阻断艾滋病毒的感染性。 如果成功完成，这些研究将使我们能够在第二阶段研究期间对该产品进行体内测试。 拟议的商业应用：Osel Inc. 提出的新方法将可作为阻止 HIV 传播的方法。 由于预计它具有成本效益，因此可以在世界范围内使用，包括在不发达国家。 该产品将作为阴道栓剂销售，每周或每月使用一次。 使用方便，女性控制。 重要的是，该产品概念与未得到满足的医疗药物和巨大的商业机会相关。