PaSAGE: PAtient Supported Approaches to Gene Editing

PaSAGE：患者支持的基因编辑方法

• 批准号: 10453979
• 负责人: Megan A. Allyse
• 金额: $ 76.04万
• 依托单位: MAYO CLINIC JACKSONVILLE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-23 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10453979
• 关键词: Address; Affect; Age of Onset; Agreement; Animal Model; Assisted Reproductive Technology; Attention; Attitude; Birth; Child; China; Clinical; Clustered Regularly Interspaced Short Palindromic Repeats; Communities; Consensus; Country; Development; Disease; Embryo; Emerging Technologies; Empirical Research; Ensure; Ethics; Event; Exercise; Family; Family member; Fetus; Future; Gene Delivery; Genes; Genetic; Genetic Diseases; Genetic Medicine; Goals; Government; Heritability; Human; Impaired cognition; In Vitro; Income; Individual; Infrastructure; International; Interview; Left; Literature; Mediating; Methods; Modeling; Mutation; Participant; Pathway interactions; Patient Representative; Patient advocacy; Patients; Penetrance; Policies; Prenatal Structures; Process; Professional Organizations; Professional Self Regulation; Protocols documentation; Published Comment; Qualitative Research; Regenerative Medicine; Regulation; Reporting; Reproductive Sciences; Research; Risk; Safety; Sampling; Science; Science Policy; Scientist; Severities; Social Values; Source; Structure; Support Groups; System; Technology; Translations; United States; United States Food and Drug Administration; Voice; Work; advocacy organizations; base; clinical application; clinical practice; clinical translation; cohort; community engaged research; deliberative democracy; design; disease-causing mutation; experimental study; falls; genetic technology; in utero; informant; innovation; member; novel; patient oriented; patient population; prenatal; prenatal intervention; pressure; progenitor; recruit; reproductive; symposium; tool

PROJECT SUMMARY/ABSTRACT The development of new methods for prenatal genetic editing in humans has accelerated the translation of technologies designed to disrupt disease mechanisms or remove disease-causing mutations entirely. These technologies show promise for preemptively addressing previously intractable genetic conditions. However, recent events have demonstrated considerable gaps in the governance structure surrounding human gene editing and its translation to clinical practice. Since the discovery that a scientist in China had conducted human experiments allegedly resulting in the birth of three genetically edited children, numerous calls have been made for a novel governance structure for prenatal human gene editing, frequently framed around moratoria or other forms of suppression, and several international bodies have convened. There has been strong pressure towards a values-based governance approach that moves beyond traditional technocratic considerations of safety and efficacy and takes into account collective normative deliberation about the ethics of prenatal intervention. This is challenging in the United States context, which is among the few high-income countries without centralized regulation of research on embryos and/or translational assisted reproductive technologies. As such, two important stakeholder voices have been largely left out of conversations around the future of prenatal gene editing in the US context: the patients and families that might be benefitted or harmed by the translation of prenatal gene editing and the scientists and clinicians who would be on the front lines of clinical translation were it to move forward. We propose to fill this gap by conducting empirical research with these key stakeholders that assesses potential governance approaches internationally and explores how they may be implemented in an United States context. The goal is to move past generalizations to explore the direct policy mechanisms that are feasible while incorporating the values and priorities of end users. This study consists of three aims. The first two, contemporaneous, aims will consist of qualitative research with two sets of stakeholders: patients and families affected by genetic conditions potentially addressable through prenatal gene editing and clinicians and scientists involved in relevant translational and clinical activities in this space. In Aim 1, We will begin by conducting a review of the international science policy landscape to gather policy mechanisms that have been proposed or implemented to manage emerging technologies in the reproductive science, genetics, and regenerative medicine spaces. We will identify policies that fall into a spectrum from permissive to restrictive. These policies will be shared with stakeholders during qualitative interviews to assess their concordance with stakeholder values and priorities. We will recruit a diverse cohort of clinicians and scientist leaders from 20 key professional societies and conduct qualitative interview to assess underlying normative underpinnings of proposed policy approaches, professional feasibility of proposals, and values and priorities around the potential translation of prenatal gene editing in humans. The results of this Aim will feed directly into the deliberative democracy exercises in Aim 3. In Aim 2, we will partner with Genetic Alliance, the largest patient advocacy organization for genetic conditions to recruit a panel of patient advisors from communities affected by 9 genetic conditions from across a spectrum of penetrance and severity. Together with the advisors we will connect with patient advocacy and support groups in these communities to recruit a cohort of patients and family members. Patients will be asked to share their understanding of the potential of gene editing, their aspirations or concerns about its clinical applications, their priorities and goals in research on their condition, and their views on the proposed policy approaches. In Aim 3 we will convene representatives from both groups, together with the research team and select policymakers to conduct two deliberative democracy exercises in which all stakeholders can deliberate towards a consensus on the appropriate mechanisms for optimal governance of prenatal gene editing technologies. The results of all three aims will be disseminated in the scientific, lay, and policy literatures.

项目总结/摘要 人类产前基因编辑新方法的发展加速了 旨在破坏疾病机制或完全消除致病突变的技术。这些 技术显示出预先解决以前棘手的遗传问题的希望。然而，在这方面， 最近的事件表明，围绕人类基因的管理结构存在相当大的差距。 编辑和翻译到临床实践。自从发现中国的一位科学家对人类进行了 据称导致三名基因编辑儿童出生的实验， 对于产前人类基因编辑的新型治理结构，经常围绕暂停或其他 各种形式的镇压，并召开了几个国际机构。有强大的压力， 一种基于价值观的治理方法，超越了传统的技术官僚式的安全考虑， 有效性，并考虑到关于产前干预伦理的集体规范性审议。这是 美国是少数几个没有中央集权的高收入国家之一， 对胚胎研究和/或辅助生殖技术转化的监管。因此，两个 重要的利益相关者的声音在很大程度上被排除在围绕产前基因的未来的对话之外。 在美国的背景下编辑：患者和家庭可能受益或受到伤害的翻译 产前基因编辑和科学家和临床医生谁将在临床翻译的第一线， 让它继续前进。我们建议通过与这些关键利益相关者进行实证研究来填补这一空白， 评估国际上可能的治理方法，并探讨如何在一个 美国背景。我们的目标是超越一般化，探索直接的政策机制， 同时结合最终用户的价值观和优先事项。 这项研究包括三个目标。前两个目标是同时发生的，将包括定性研究， 两组利益相关者：受遗传疾病影响的患者和家庭， 产前基因编辑和临床医生和科学家参与相关的翻译和临床活动， 空间在目标1中，我们将开始对国际科学政策格局进行审查， 为管理新兴技术而提出或实施的政策机制， 生殖科学、遗传学和再生医学领域。我们将确定属于 从允许到限制的范围。这些政策将在定性分析期间与利益攸关方分享。 访谈，以评估其与利益相关者价值观和优先事项的一致性。我们将招募一批不同的 来自20个主要专业学会的临床医生和科学家领导人，并进行定性访谈，以评估 拟议政策办法的基本规范基础，建议的专业可行性，以及 价值和优先事项围绕产前基因编辑在人类中的潜在翻译。这一目标的结果 将直接纳入目标3中的协商民主实践。在目标2中，我们将与Genetic合作 联盟，最大的病人倡导组织的遗传条件，招募一个小组的病人顾问 来自受9种遗传病影响的社区，这些遗传病的严重程度和严重程度各不相同。一起 我们将与这些社区的患者倡导和支持团体联系， 患者和家属的队列。患者将被要求分享他们对潜在的 基因编辑，他们对其临床应用的愿望或担忧，他们在研究中的优先事项和目标， 他们的状况，以及他们对拟议政策方针的看法。在目标3中，我们将召集代表 从这两个群体中，与研究团队一起，选择政策制定者进行两次审议， 民主活动，所有利益攸关方都可以就适当的 产前基因编辑技术的最佳治理机制。所有三个目标的结果将是 在科学、非专业和政策文献中传播。