SBIR Phase I: Intracellular Delivery for Rapid Point-of-Care Labeling of Therapeutic Cells

小型企业创新研究(SBIR)第一阶段项目的更广泛影响/商业潜力包括利用创新方法更有效地提供和监测治疗药物。对免疫和干细胞疗法的实时监测和跟踪还处于初级阶段。然而，如果不能准确地知道治疗细胞的位置，临床医生就无法评估安全性、设计最佳剂量或做出与治疗方法相关的临床决策。随着数十亿美元的细胞治疗市场在竞相开发下一代挽救生命、成本效益高、毒性较低的细胞治疗产品，对安全风险管理的要求越来越高，以监测患者体内细胞产品的靶向和肿瘤递送。这项建议解决了细胞和基因治疗行业中尚未满足的一个关键需求，即特别是为了能够在体内进行跟踪而对治疗细胞进行快速护理点标记。到2024年，在美国涉及治疗性细胞的临床试验中，临床前和临床细胞跟踪的潜在市场估计将达到约11.4亿美元。这个小企业创新研究(SBIR)第一阶段项目涉及一种创新的细胞内输送方法，其中机械操作或细胞挤压只需通过位于设计用于在离心机(旋转柱)中处理的柱中的专有机械操作元件来推动细胞，在外源货物存在的情况下即可实现。与传统和微流控方法相比，最终用户将意识到细胞内给药的显著优势，包括：1)方便的旋转柱形式；2)细胞处理时间短；3)易于放大和多路传输；4)适用于多种细胞类型；以及5)与自动化/机器人细胞生产系统兼容，包括为临床设计的自体细胞生产系统。提出了三个目标，涉及原型自旋柱的产生及其在优化元件设计方面的应用，以提供高效的分子间传递铁基纳米颗粒(磁共振成像造影剂)到T细胞和间充质干细胞。这项研究将实现治疗和再生细胞的快速护理点标记，用于体内跟踪，使临床医生能够及时做出关于治疗策略的决定，从而确保更好的临床结果。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。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project involves leveraging an innovative approach to deliver and monitor therapeutics more effectively. Real-time monitoring and tracking of immune and stem cell therapies is in its infancy. However, without the capability to precisely know where therapeutic cells localize, clinicians cannot assess safety, design optimal doses, or make clinical decisions related to therapeutic approaches. As the multi-billion-dollar cell therapy market is expanding rapidly in its race to develop the next generation of life-saving, cost-effective, lower toxicity cell therapy products there is a heightened requirement for safety risk management to monitor on-target, on-tumor delivery of cell products in patients. This proposal addresses a critical unmet need in the cell and gene therapy industry for rapid point-of-care labeling of therapeutic cells specifically to enable tracking in the body. The addressable market for preclinical and clinical cell tracking in clinical trials involving therapeutic cells in the United States is estimated to reach approximately $1.14 billion by 2024.This Small Business Innovation Research (SBIR) Phase I project involves an innovative approach to intracellular delivery where mechanoporation or cell-squeezing is achieved simply by propelling cells, in the presence of exogeneous cargo, through a proprietary mechanoporation element that resides in a column designed to be processed in a centrifuge (spin column). End users will realize significant advantages over conventional and microfluidic approaches to intracellular delivery including: 1) Convenient spin column format; 2) Short cell processing times; 3) Ease of scale-up and multiplexing; 4) Applicability to numerous cell types; and 5) Compatibility with automated/robotic cell production systems including autologous cell production systems designed for clinical settings. Three objectives are proposed involving the generation of prototype spin columns and their use in optimizing aspects of element design to afford efficient intermolecular delivery of iron-based nanoparticles (magnetic resonance imaging contrast agent) into T-cells and Mesenchymal Stem Cells. The study will enable rapid point-of-care labeling of therapeutic and regenerative cells for in vivo tracking, empowering clinicians to make timely decisions with respect to treatment strategies, thus ensuring better clinical outcomes.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.