Use of Modified Lactobacilli to Block HIV Transmission

描述：(申请人提供)OSEL成立的目的是开发和 将一种防止艾滋病毒经阴道传播的新方法商业化。我们建议 用非致病乳杆菌从基因上定植阴道粘膜 经过修改以结合和灭活艾滋病毒。我们正在构建重组 表达有效的艾滋病毒抑制物氰基韦林-N(CV-N)的乳杆菌，或 相关的HIV结合蛋白。乳酸菌L.jensenii是一种 优秀的人类阴道定殖者，我们已经获得了初步证据 我们可以操纵这个菌株在细菌上表达外源蛋白。 浮出水面。我们正在使用一种新的、强大的乳酸菌特异性启动子来驱动 以表面锚定或分泌型蛋白的形式表达CV-N。因此， 这种有效的HIV抑制物在修饰细菌中的表达应该 减少或消除由精液引入的艾滋病毒颗粒，从而显著 降低艾滋病毒传播的风险。这种方法将是离散的， 由女性控制，并应与疫苗、避孕套或 其他潜在的保护方法。Osel提出的工作包括 简氏乳杆菌的遗传修饰及证明 生物工程菌能够在体外阻断艾滋病毒的传染性。 拟议的商业应用：迫切需要新的方法来阻断艾滋病毒等病毒的传播。Osel公司提出的这一新方法将直接用于阻断HIV的传播。由于预计它具有成本效益，它可以在世界各地使用，包括在不发达国家。该产品将以阴道栓剂的形式上市，每周或每月使用一次，使用方便，女性控制。重要的是，本申请中提出的研究直接涉及与未得到满足的医疗需求和大量商业机会相关的产品概念。

DESCRIPTION: (Provided by Applicant) Osel was founded to develop and commercialize a novel approach to prevent vaginal HIV transmission. We propose to colonize the vaginal mucosa with non-pathogenic lactobacilli, genetically modified to bind and inactivate HIV. We are constructing recombinant lactobacilli that express the potent HIV-inhibitor, cyanovirin-N (CV-N), or related HIV binding proteins. The strain of lactobacillus, L. jensenii, is an excellent human vaginal colonizer and we have gained preliminary evidence that we can manipulate this strain to express foreign proteins on the bacterial surface. We are using a new, strong, lactobacillus-specific promoter to drive expression of CV-N as a surface-anchored or secreted protein. Thus, the expression of this potent HIV-inhibitor from the modified bacteria should reduce or eliminate HIV particles introduced by semen, thereby significantly reducing the risk of HIV transmission. This approach would be discrete, female-controlled and should act synergistically with vaccines, condoms or other potential methods of protection. The work being proposed by Osel includes the genetic modifications of L. jensenii and demonstration that the bioengineered bacteria are capable of blocking HIV-infectivity in vitro. PROPOSED COMMERCIAL APPLICATION: New approaches to block the transmission of viruses, like HIV, are urgently needed. The novel aproach proposed by Osel Inc. would find direct utility as a method to block HIV transmission. Since it is anticipated to be cost-effective, it can be used throughout the world, including in underdeveloped countries. The product will be marketed as a vaginal suppository to be used on a weekly, or monthly basis, and will be convenient to use and female-controlled. Importantly, the studies proposed in this application relate directly to a product concept associated with an unmet medical need and substantial commercial opportunity.