Display of HIV Binding Proteins on Bacterial S-Layers

描述（由申请人提供）：Osel Inc.正在努力开发一种新的方法来预防艾滋病毒的阴道传播。 这种方法涉及对非致病性细菌进行遗传修饰，类似于在粘膜表面发现的那些细菌，以产生具有结合、捕获和抑制HIV的能力的分子。 通过用这些细菌定殖阴道腔，HIV将对修饰的细菌具有与宿主细胞相同的亲和力。 HIV与这些经过修饰的细菌的结合应该会阻止病毒随后传播给宿主。 如本申请中所概述的，我们提出工程改造特定的阴道来源的大肠杆菌菌株，L. crispatus，以表达高亲和力的HIV结合蛋白。 自L.由于卷曲的阴道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，从而定位这些分子，以便在引入阴道腔时随时接近HIV。 在这些I期研究中，我们将对这些细菌进行遗传修饰，使其在S层的各个结构域中显示HIV结合配体。 我们随后将证明这些修饰的细菌在体外阻断HIV感染性。 如果成功完成，这些研究将使我们能够在II期研究期间对该产品进行体内试验。 拟议的商业应用：Osel Inc.提出的新方法。会被用作阻止艾滋病传播的方法。 由于预计它具有成本效益，因此可以在全世界使用，包括在欠发达国家使用。 本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，该产品概念与未满足的医疗需求和巨大的商业机会相关。

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.