PaSAGE: PAtient Supported Approaches to Gene Editing

PaSAGE：患者支持的基因编辑方法

• 批准号: 10709501
• 负责人: Megan A. Allyse
• 金额: $ 63.73万
• 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/10709501
• 关键词: Acceleration; 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; 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; Policy Maker; 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; aspirate; 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; permissiveness; prenatal; prenatal intervention; pressure; progenitor; recruit; reproductive; symposium; tool; translational potential

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.

项目概要/摘要 人类产前基因编辑新方法的开发加速了基因编辑的转化 旨在破坏疾病机制或完全消除致病突变的技术。这些 技术有望先发制人地解决以前棘手的遗传问题。然而， 最近发生的事件表明，围绕人类基因的治理结构存在巨大差距 编辑及其转化为临床实践。自从发现一位中国科学家对人类进行了 据称实验导致三名基因编辑儿童的诞生，已接到无数电话 寻求一种新颖的产前人类基因编辑治理结构，通常以暂停或其他方式为框架 各种形式的镇压，多个国际机构已召开会议。受到了强大的压力 基于价值观的治理方法，超越了传统的技术官僚对安全和安全的考虑 功效并考虑到有关产前干预伦理的集体规范审议。这是 美国是少数几个没有集中化的高收入国家之一 胚胎和/或转化辅助生殖技术研究的监管。因此，两个 重要利益相关者的声音在很大程度上被排除在有关产前基因未来的讨论之外 在美国背景下的编辑：患者和家庭可能因翻译而受益或受到伤害 产前基因编辑以及将处于临床转化第一线的科学家和临床医生 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 评估国际上潜在的治理方法，并探讨如何在全球范围内实施这些方法 美国背景。目标是超越概括，探索直接政策机制 可行，同时纳入最终用户的价值观和优先事项。 这项研究包括三个目标。前两个同时期的目标将包括定性研究 两类利益相关者：受遗传病影响的患者和家庭，可通过以下方式解决 产前基因编辑以及参与相关转化和临床活动的临床医生和科学家 空间。在目标 1 中，我们将首先对国际科学政策格局进行审查，以收集 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。我们将确定属于以下范围的政策 从宽松到限制的范围。这些政策将在定性期间与利益相关者分享 访谈以评估其与利益相关者价值观和优先事项的一致性。我们将招募多元化的人才 来自20个主要专业协会的临床医生和科学家领导者进行定性访谈以评估 拟议政策方法的基本规范基础、提案的专业可行性，以及 围绕人类产前基因编辑潜在转化的价值观和优先事项。这一目标的结果 将直接融入目标 3 中的协商民主实践。在目标 2 中，我们将与 Genetic 联盟，最大的遗传疾病患者倡导组织，招募患者顾问小组 来自受 9 种遗传病影响的社区，这些遗传病的外显率和严重程度各不相同。一起 我们将与顾问一起与这些社区的患者倡导和支持团体联系，招募 患者及其家属队列。将要求患者分享他们对潜力的理解 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 两个小组与研究团队和选定的政策制定者一起进行两次审议 民主活动，所有利益攸关方都可以商议就适当的事项达成共识 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。