Developing second generation SCID pig models: filling the gaps to improve translation of therapeutics in regenerative medicine

开发第二代 SCID 猪模型：填补空白，改善再生医学疗法的转化

• 批准号: 10405974
• 负责人: Christopher Tuggle
• 金额: $ 24.54万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-15 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10405974
• 关键词: Address; Age; Animal Model; Animals; Canada; Cells; Client; Clinic; Collaborations; Communication; Communities; Custom; Data; Development; Disease; Equipment; Family suidae; Funding; Future; Generations; Goals; Health; Hematopoiesis; Housing; Human; Human Biology; Hydrogen Peroxide; IL2RG gene; Immune; Industry; Industry Standard; Institution; Knowledge; Location; Methods; Modeling; Monoclonal Antibody R24; Mus; Neonatal; Operative Surgical Procedures; Pre-Clinical Model; Preclinical Testing; Preparation; Procedures; Protocols documentation; Recording of previous events; Regenerative Medicine; Reporting; Research; Research Personnel; Scientist; Ships; Site; Sterility; Sterilization; System; Testing; Therapeutic; Tissues; Translations; Transportation; United States; Vaporizer; Work; Xenograft procedure; artemis; biocontainment facility; biosecurity; design; experience; high efficiency particulate air filter; human model; improved; interest; method development; mutant; novel; parent grant; porcine model; pre-clinical; pre-clinical research; pregnant; research study; safety study; stem cell therapy; stem cells; translational model; transplant model

Project Summary/Abstract Large animal models are critically needed to develop regenerative medicine therapeutics and maximize safe translation to the clinic, as the FDA recommends data be provided on both small and large animal models for approval of such therapies. Using R24 funding (OD019813), we developed biocontainment facilities and protocols to raise an Artemis (DCLRE1C) mutant SCID pig model (ART) as well as an improved model also mutant in IL2RG (ART-IL2RG). The use of SCID pig models in preclinical research necessitates the ability to safely ship healthy SCID pigs across the United States to interested scientists who do not have the ability to raise such pigs themselves. The following two Aims address this existing deficit in the SCID pig research field: Aim 1. Create methods to safely transport SCID pigs within a HEPA filtered isolator transported in a HEPA filtered trailer to researchers in the US and Canada Aim 2. Improve the biosecurity and health of SCID pigs by creating a shower-in facility and purchase dedicated sterilization equipment. As there is no established method to ship SCID pigs while maintaining biocontainment, work in Aim 1 will focus on development of a transportation system consisting of a customized trailer and internal isolators will make this critical next step possible. The transportable internal isolators are needed both to safely house the SCID pigs as well as short- distance transportation from facility biocontainment bubbles to the sterilized trailer for long-distance transport. Further, this revised plan expands the type of clientele who can use the SCID pig, as the isolators containing the SCID pig can be maintained at an external site for short-term research studies. In Aim 2, we continue to develop effective protocols for SCID pig rearing and have identified that isolators are a useful adjunct to the originally proposed and validated bubble procedures. Biosecurity of the SCID pigs will be dramatically improved by the addition of a shower-in facility and purchase of dedicated hydrogen peroxide vaporizer adequately sized for sterilizing these new spaces and equipment. We propose to use A&R funds to renovate unused space adjacent to the existing biocontainment bubbles to provide this shower-in facility and raise the level of biosecurity for SCID pig housing to the industry standard. The sterilization equipment, consisting of a dedicated hydrogen peroxide vaporizer capable of handling the existing bubbles and the proposed new transportation approach in Aim 1, is critically needed as existing equipment is inadequate. The proposed Supplemental Aims do not expand the scope of the existing parent grant and are directly responsive to the call for A&R supplements.

项目概要/摘要 开发再生医学疗法和最大限度地提高安全转化迫切需要大型动物模型 到诊所，因为 FDA 建议提供小型和大型动物模型的数据以批准此类 疗法。利用 R24 资金 (OD019813)，我们开发了生物防护设施和协议来饲养 Artemis (DCLRE1C) 突变 SCID 猪模型 (ART) 以及 IL2RG 突变的改进模型 (ART-IL2RG)。 SCID的使用 临床前研究中的猪模型需要能够将健康的 SCID 猪安全地运送到美国各地 那些没有能力自己饲养这种猪的科学家感兴趣。以下两个目标解决了这个问题 SCID猪研究领域现有的缺陷： 目标 1. 创建在 HEPA 过滤隔离器内安全运输 SCID 猪的方法 给美国和加拿大研究人员的预告片 目标 2. 通过创建淋浴设施并购买专用淋浴设施来改善 SCID 猪的生物安全和健康 灭菌设备。 由于没有既定方法在保持生物防护的同时运输 SCID 生猪，目标 1 的工作将集中于 开发由定制拖车和内部隔离器组成的运输系统将使这一点变得至关重要 下一步可能。需要可移动的内部隔离器来安全地安置 SCID 猪以及短期内 从设施生物防护罩到用于长途运输的消毒拖车的距离运输。 此外，此修订计划扩大了可以使用 SCID 猪的客户类型，因为隔离器包含 SCID 猪 可以保存在外部站点以进行短期研究。在目标 2 中，我们继续开发有效的 SCID 养猪方案并已确定隔离器是最初提出和 经过验证的气泡程序。通过增加淋浴间，SCID 猪的生物安全性将得到显着改善 设施并购买尺寸足够大的专用过氧化氢蒸发器，用于对这些新空间进行消毒，以及 设备。我们建议使用 A&R 资金来翻新现有生物防护气泡附近的未使用空间，以 提供该淋浴设施，并将 SCID 猪舍的生物安全水平提高到行业标准。这 灭菌设备，包括能够处理现有气泡的专用过氧化氢蒸发器 由于现有设备不足，迫切需要目标 1 中拟议的新运输方法。这 拟议的补充目标不会扩大现有母基金的范围，而是直接响应号召 用于 A&R 补充剂。