SBIR Phase I: Horizontal genomic transfer technology: Bioengineering DNA sequences for the creation of a non-viral targeted cancer cell specific gene therapy platform

SBIR 第一阶段：水平基因组转移技术：生物工程 DNA 序列，用于创建非病毒靶向癌细胞特异性基因治疗平台

• 批准号: 2103565
• 负责人: Stephen Chang
• 金额: $ 25.58万
• 依托单位: KODIKAZ THERAPEUTIC SOLUTIONS, INC.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2022-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2103565&HistoricalAwards=false
• 关键词: SBIR; Phase; Horizontal; genomic; transfer

The broader impact /commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to improve clinical outcomes for cancer treatment. Horizontal genomic transfer (HGT) has the potential to deliver a variety of lethal payloads to tumors with high specificity. The proposed platform will enable better cancer therapies with lower side effects. To accelerate translation, this project proposes the development of a high-throughput platform to enable the evaluation of the specificity, lethality, and efficiency of therapies based on HGT across many different cell types, multiple dosing and many other variables. These defining features of the proposed HGT platform will permit the rapid and cost-effective development of novel gene therapies to improve patient care. This Small Business Innovation Research Phase I project aims to create a framework for the rapid high-throughput screening of cell-specific HGT-based therapeutics. HGT was previously thought to only be present in species like bacteria and fungi, but has recently been discovered in human cancer cells. Preliminary data has demonstrated the HGT’s abilities to deliver different expression vectors in animal models and in culture, but the efficiency of delivery and expression is currently unknown. This project will interrogate identified HGT and their sequences in the lab to better understand how to further optimize them to maximize delivery and expression of genomic payloads. The first aim proposes the development of the high-throughput screening platform for assessing integration and expression efficiency of HGT, and the second aim proposes the correlation of flow cytometry data with HGT integration into the tumor cell genome. Successful completion of the project will inform HGT platform development to evaluate numerous cellular parameters simultaneously and ultimately accelerate product development for cancer therapies and potentially in other indications.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)第一阶段项目的更广泛的影响/商业潜力是改善癌症治疗的临床结果。水平基因组转移(HGT)具有很高的特异性，可以将多种致死有效载荷传递给肿瘤。拟议的平台将以更低的副作用实现更好的癌症治疗。为了加速翻译，该项目建议开发一个高通量平台，以便能够评估基于HGT的治疗的特异性、致命性和效率，涉及许多不同的细胞类型、多次给药和许多其他变量。拟议的HGT平台的这些明确特征将允许快速和具有成本效益的新基因疗法的开发，以改善患者护理。这个小型企业创新研究第一阶段项目旨在为细胞特异性HGT疗法的快速高通量筛选创建一个框架。HGT之前被认为只存在于细菌和真菌等物种中，但最近在人类癌细胞中发现了HGT。初步数据已经证明，hGT能够在动物模型和培养中传递不同的表达载体，但传递和表达的效率目前尚不清楚。该项目将在实验室中询问已识别的HGT及其序列，以更好地了解如何进一步优化它们，以最大限度地提高基因组有效载荷的传递和表达。第一个目的是开发用于评估HGT整合和表达效率的高通量筛选平台，第二个目的是提出流式细胞仪数据与HGT整合到肿瘤细胞基因组的相关性。该项目的成功完成将为HGT平台的开发提供信息，以同时评估众多细胞参数，并最终加速癌症治疗的产品开发，并可能用于其他指标。该奖项反映了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。