National Ferret Research and Resource Institute (NFRRI) at University of Iowa

虽然遗传小鼠模型在过去四年中一直是转化生物医学研究的支柱， 几十年来，由于小鼠细胞生物学的物种特异性差异，小鼠经常无法模拟人类疾病。 受影响的器官，以及它们基因组的进化分歧。雪貂已经被证明是 用于模拟传染病（包括SARS-CoV 2）和人类脑、胰腺、 和肺的功能。爱荷华州大学（UI）是世界上唯一一个能够从基因上 对雪貂进行基因工程改造，使其具有多种精确的基因改变，而这些基因改变以前只能在小鼠中实现。这项技术 使得能够构建能够对干细胞区室进行命运作图的遗传雪貂模型（即， 谱系追踪）、对人类疾病（包括具有人源化遗传基因座的疾病）进行建模以及条件遗传学 使用Cre重组酶。一个由联邦政府资助的国家雪貂研究和资源中心成立了八个 多年前，该公司为创造新的遗传雪貂模型提供服务， 雪貂，以及现有遗传系的组织和细胞的分布。这种国家资源提供了 为超过129名学术研究人员提供服务，其中108名在UI之外，目前有8份合同 生物技术公司正在寻求利用雪貂来开发遗传和后天疾病的疗法， 模型这些服务已经超过了对雪貂进行研究的设施的能力， 在加州大学校园里养雪貂该提案旨在设计和建造一个研究设施， 国家雪貂研究和资源研究所（NFRRI）在UI校园。拟议的设施已 旨在最大限度地发挥协同作用，最大限度地减少与UI现有设施的重叠， 连接到现有的雪貂扩展住房（称为BSRF设施）。NFRRI将包含国家- 用于雪貂受精卵基因工程和雪貂研究的最先进设备。程序 空间将包括一个符合美国农业部标准的无菌手术室和单独的显微注射室，用于模型创建。 除了湿实验室研究空间，专门的程序套房将容纳雾化，肺 功能测试和专门的成像设备。NFRRI将主要为学术界提供服务。 UI和营利性生物技术公司以外的调查人员，但也将提供雪貂模型进行研究 这将发生在现有的研究设施的主UI校园。此外，选择的地点为 该设施拥有毗邻的土地，用于未来扩展研究空间和雪貂住房，具有长期战略意义。 计划招募NFRRI的下一代领导人，并利用与营利性组织的现有关系 寻求在临床前雪貂模型中开发人类疾病疗法的生物技术公司。的 NFRRI的短期和长期战略目标将通过与 爱荷华州大学（NFRRI大楼的费用分摊）、囊性纤维化基金会和马歇尔农场（ 研究用雪貂的最大饲养者）。

While genetic mouse models have been the backbone of translational biomedical research for the past four decades, mice often fail to model human disease due to species-specific differences in the cell biology of the affected organs, as well as the evolutionary divergence of their genome. The ferret has proven an excellent species for modeling infectious disease (including SARS-CoV2) and human diseases of the brain, pancreas, and lung when mice have failed. The University of Iowa (UI) is the only location in the world capable of genetically engineering ferrets with multiple precise genetic alterations previously only achievable in mice. This technology has enabled the construction of genetic ferret models capable of fate mapping stem cell compartments (i.e., lineage tracing), modeling human diseases including those with humanized genetic loci, and conditional genetics using Cre recombinase. A federally-funded National Ferret Research and Resource Center was formed eight years ago, which provides services for the creation of new genetic ferret models, performing research studies in ferrets, and the distribution of tissues and cells from existing genetic lines. This national resource has provided services to more than 129 academic investigators,108 of which are outside the UI, and currently has 8 contracts with biotechnology companies seeking to develop therapies for genetic and acquired diseases using ferret models. These services have exceeded the capacity of facilities for both performing research in ferrets and housing ferrets on the UI campus. This proposal seeks to design and construct a research facility that will house the National Ferret Research and Resource Institute (NFRRI) on the UI campus. The proposed facility has been designed to maximize synergy and minimize overlap with existing facilities at UI and will be adjacent and connected to existing ferret expansion housing (referred to as the BSRF facility). The NFRRI will contain state- of-the-art equipment for genetically engineering ferret zygotes and performing research in ferrets. Procedural space will include a USDA-compliant sterile surgical suite and separate microinjection room for model creation. In addition to wet lab research space, specialized procedural suites will accommodate nebulization, pulmonary function testing, and specialized imaging equipment. The NFRRI will primarily provide services to academic investigators outside UI and for-profit biotechnology companies, but will also provide ferret models for research that will occur on the main UI campus in existing research facilities. Furthermore, the chosen location for the facility has adjacent land for future expansion of research space and ferret housing with a long-term strategic plan that recruits next-generation leaders of the NFRRI and capitalizes on existing relationships with for-profit biotechnology companies seeking to develop therapies for human diseases in preclinical ferret models. The short- and long-term strategic goals of the NFRRI will be facilitated through financial partnerships with the University of Iowa (cost sharing of the NFRRI building), Cystic Fibrosis Foundation, and Marshall Farms (the largest breeder of ferrets for research).