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

这个小企业创新研究（SBIR）一期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）有可能以高特异性向肿瘤传递各种致命的有效载荷。提出的平台将实现更好的癌症治疗和更低的副作用。为了加速转化，该项目建议开发一个高通量平台，以评估基于HGT的治疗方法在许多不同细胞类型、多种剂量和许多其他变量中的特异性、致命性和效率。提议的HGT平台的这些定义特征将允许快速和具有成本效益的新型基因疗法的发展，以改善患者的护理。这个小企业创新研究第一阶段项目旨在创建一个快速高通量筛选细胞特异性hgt治疗方法的框架。HGT以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被发现。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，但目前尚不清楚其传递和表达的效率。该项目将在实验室中研究已确定的HGT及其序列，以更好地了解如何进一步优化它们，以最大限度地实现基因组有效载荷的传递和表达。第一个目标是建立高通量筛选平台来评估HGT的整合和表达效率，第二个目标是将流式细胞术数据与HGT整合到肿瘤细胞基因组中的相关性。该项目的成功完成将为HGT平台的开发提供信息，以同时评估多种细胞参数，并最终加速癌症治疗和其他适应症的产品开发。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.