SBIR Phase I: Investigation of a Bioengineered Immunotoxin for Use as a Biopesticide for the Control of Aquatic Invasive Mussel Infestation

SBIR 第一阶段：研究用作控制水生入侵贻贝感染的生物农药的生物工程免疫毒素

• 批准号: 1938619
• 负责人: John Higley
• 金额: $ 22.5万
• 依托单位: EQO, INC.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-10-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1938619&HistoricalAwards=false
• 关键词: SBIR; Phase; Investigation; Bioengineered; Immunotoxin

The broader impact & commercial potential of this Small Business Innovation Research (SBIR) project is the ability to control zebra & quagga mussel infestations with a cost-effective and target-specific biological treatment. In addition to the estimated $7 billion economic impact, mussel infestation causes substantial ecological impacts. Currently, there is no treatment option available following infestation by quagga or zebra mussels functional at the scale of commercial reservoirs without significant disruption of native species. The successful development of an efficient and specific treatment has the potential to improve the ability to restore and protect native aquatic ecosystems, water infrastructure, power production infrastructure, and native fisheries. Additionally, the approach has the potential to lower production cost, and require a lower effective dose when compared to current treatment options. This SBIR Phase I project proposes to develop a biopesticide comprised of the enzymatic portion of a toxin for the mechanism of action and the binding domains from antibodies for targeting zebra and quagga mussels. Control of infestation by chemical means is largely restricted to enclosed systems, and requires additional remediation prior to water use. Biopesticides, however, can be considered a reduced risk treatment option. The use of ScFv (single chain variable fragment regions) from mAbs (monoclonal antibodies) has become common place in pharmaceuticals like Herceptin and MT-3724 and can be used here, resulting in a treatment product with anticipated high specificity, high efficiency, known mechanism of action, limited half-life, no expected long-term environmental impact, and limited to absent off-target impact. This work is believed to be novel as biopesticides utilizing immunotoxin technology for the remediation of aquatic nuisance species are not well developed.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这个小型企业创新研究(SBIR)项目的更广泛的影响和商业潜力是能够通过具有成本效益的和目标特定的生物处理来控制斑马和斑羚贻贝的侵扰。除了估计70亿美元的经济影响外，贻贝感染还会造成重大的生态影响。目前，在商业水库规模的功能性Quagga或斑马贻贝侵扰后，没有可用的治疗方案，而不会对当地物种造成重大破坏。成功开发有效和具体的处理方法有可能提高恢复和保护当地水生生态系统、水基础设施、电力生产基础设施和当地渔业的能力。此外，该方法有可能降低生产成本，与目前的治疗方案相比，需要更低的有效剂量。这项SBIR第一阶段项目建议开发一种生物杀虫剂，由作用机制所需的毒素的酶部分和针对斑马和Quagga贻贝的抗体的结合域组成。通过化学手段控制虫害在很大程度上限于封闭的系统，在用水之前需要额外的补救措施。然而，生物农药可以被认为是一种风险较低的治疗选择。单抗的单链可变区(Single Chain Variable Fragage Region，ScFv)在赫赛汀(Herceptin)和MT-3724等药物中的应用已十分普遍，并可在此使用，从而产生一种预期的高特异性、高效率、已知的作用机制、有限的半衰期、无预期的长期环境影响、以及仅限于无靶标影响的治疗产品。这项工作被认为是新颖的，因为利用免疫毒素技术修复水生有害物种的生物杀虫剂还没有得到很好的开发。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。