Superovulation without hormones - developing a novel, non-invasive method to induce follicular growth

无激素超数排卵——开发一种新颖的非侵入性方法来诱导卵泡生长

• 批准号: 105775
• 金额: $ 81.17万
• 依托单位: OSTARA BIOMEDICAL LIMITED
• 依托单位国家: 英国
• 项目类别: Study
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=105775
• 关键词: Superovulation; without; hormones; developing; novel

The creation of genetically modified (transgenic) animal models, primarily mice and rats, has revolutionised our understanding of human disease. Transgenic biotechnologies utilise large numbers of animals: both females and males to generate embryos for genetic manipulation, females to provide a host uterus to support the development of transgenic embryos, and infertile males to induce so-called 'pseudopregnancy' (a process by which females' uterus becomes receptive to transferred embryos) in recipient females. In 2017, 1.69 million UK Home Office regulated procedures were conducted on mice destined for use in such transgenic breeding programmes. Therefore, there is a great market demand for new technologies which can both improve procedural efficiency and markedly reduce experimental animal pain and distress.Mouse embryos for research/breeding programmes are generated using donor females by a process known as superovulation, which aims to maximise oocyte/embryo yield per female. Currently, the procedure involves injecting hormones into the abdominal cavity of female mice to stimulate the growth of ovarian follicles and eggs. The latter are subsequently either fertilised through natural mating or harvested and fertilised in vitro. However, successful superovulation is inherently variable, with yields and quality varying across different operators and batches of hormones. Moreover, intra-abdominal injections are painful and distressing for animals such that users have an ethical and legal responsibility under the 3Rs principles ('Replacement, Reduction, Refinement') to use alternative methods if available.Ostara have identified a market opportunity for developing a high-quality replacement for the hormones used in superovulation (using small molecules called aptamers) as well as moving away from intra-abdominal injections by delivering their active agents vaginally (which is not achievable using current hormone treatments). This novel approach can significantly improve the reliability of superovulation through the use of quality-controlled metered dose hormone alternatives whilst reducing pain and distress by using a minimally invasive agent delivery route.

转基因动物模型（主要是小鼠和大鼠）的创建彻底改变了我们对人类疾病的理解。转基因生物技术利用大量动物：雌性和雄性都产生用于基因操作的胚胎，雌性提供宿主子宫以支持转基因胚胎的发育，而不育的雄性在受体雌性中诱导所谓的“假怀孕”（雌性子宫接受移植胚胎的过程）。2017年，英国内政部对用于此类转基因育种计划的小鼠进行了169万次监管程序。因此，对既能提高操作效率又能显著减少实验动物疼痛和困扰的新技术有很大的市场需求。用于研究/育种项目的小鼠胚胎是通过一种称为超排卵的过程使用雌性供体产生的，该过程旨在最大限度地提高每只雌性的卵母细胞/胚胎产量。目前，该方法包括向雌性小鼠腹腔注射激素，以刺激卵巢卵泡和卵子的生长。后者随后要么通过自然交配受精，要么收获并在体外受精。然而，成功的超排卵本质上是可变的，其产量和质量因不同的操作者和不同批次的激素而异。此外，腹腔内注射对动物来说是痛苦和痛苦的，因此使用者有道德和法律责任，根据3Rs原则（“替代，减少，改进”），在可行的情况下使用替代方法。Ostara已经发现了一个市场机会，即开发一种用于超排卵的激素的高质量替代品（使用称为适体体的小分子），以及通过阴道输送活性药物来摆脱腹腔注射（目前的激素治疗方法无法实现）。这种新方法可以通过使用质量控制的计量激素替代品显著提高超排卵的可靠性，同时通过使用微创药物递送途径减少疼痛和痛苦。