寡核苷酸的发育和生殖毒性测试策略:研讨会论文集。

IF 4.7 2区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Nucleic acid therapeutics Pub Date : 2025-06-01 Epub Date: 2025-05-30 DOI:10.1089/nat.2025.0013
Bethany R Hannas, Sara M Bender, Eileen Blasi, Christopher J Bowman, Joy A Cavagnaro, Connie L Chen, Pragati S Coder, Britt Duijndam, Alan Hoberman, Tae-Won Kim, Isabelle Leconte, Kazushige Maki, Mineo Matsumoto, Fumito Mikashima, Dinah L Misner, Lutz Mueller, Nicola Powles-Glover, Stephanie Rayhon, Camelia Saffarini, Christine Siezen, Jennifer Sisler, Ronald L Wange, Tacey White, Michael V Templin
{"title":"寡核苷酸的发育和生殖毒性测试策略:研讨会论文集。","authors":"Bethany R Hannas, Sara M Bender, Eileen Blasi, Christopher J Bowman, Joy A Cavagnaro, Connie L Chen, Pragati S Coder, Britt Duijndam, Alan Hoberman, Tae-Won Kim, Isabelle Leconte, Kazushige Maki, Mineo Matsumoto, Fumito Mikashima, Dinah L Misner, Lutz Mueller, Nicola Powles-Glover, Stephanie Rayhon, Camelia Saffarini, Christine Siezen, Jennifer Sisler, Ronald L Wange, Tacey White, Michael V Templin","doi":"10.1089/nat.2025.0013","DOIUrl":null,"url":null,"abstract":"<p><p>A 2023 workshop brought together stakeholders involved in the development and safety assessment of oligonucleotide (ONT) therapeutics. The purpose was to discuss potential strategies and opportunities for enhancing developmental and reproductive toxicity (DART) assessment of ONTs. The workshop was timely, bringing together regulators, industry representatives, consultants, and contract research organization partners interested in the ongoing development of internationally harmonized guidance for nonclinical safety assessment of ONTs. Given DART's importance in nonclinical safety assessment and the unique attributes of ONTs, the forum discussed case studies, consensus approaches, and areas needing further development to optimize DART strategies. This report covers the workshop proceedings, highlighting methods to achieve a robust DART assessment for ONTs. It includes case studies that described strategies for dose level selection, dosing frequency, species selection, and alternative animal model approaches. Topics also cover surrogate ONT use, exposure of the placenta and embryo/fetal compartment, and weight of evidence approaches. A goal of these workshop proceedings is to describe example approaches to hopefully inform the DART strategy expectations in the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidance currently under development for nonclinical safety assessment of ONTs.</p>","PeriodicalId":19412,"journal":{"name":"Nucleic acid therapeutics","volume":" ","pages":"93-113"},"PeriodicalIF":4.7000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Developmental and Reproductive Toxicity Testing Strategies for Oligonucleotides: A Workshop Proceedings.\",\"authors\":\"Bethany R Hannas, Sara M Bender, Eileen Blasi, Christopher J Bowman, Joy A Cavagnaro, Connie L Chen, Pragati S Coder, Britt Duijndam, Alan Hoberman, Tae-Won Kim, Isabelle Leconte, Kazushige Maki, Mineo Matsumoto, Fumito Mikashima, Dinah L Misner, Lutz Mueller, Nicola Powles-Glover, Stephanie Rayhon, Camelia Saffarini, Christine Siezen, Jennifer Sisler, Ronald L Wange, Tacey White, Michael V Templin\",\"doi\":\"10.1089/nat.2025.0013\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>A 2023 workshop brought together stakeholders involved in the development and safety assessment of oligonucleotide (ONT) therapeutics. The purpose was to discuss potential strategies and opportunities for enhancing developmental and reproductive toxicity (DART) assessment of ONTs. The workshop was timely, bringing together regulators, industry representatives, consultants, and contract research organization partners interested in the ongoing development of internationally harmonized guidance for nonclinical safety assessment of ONTs. Given DART's importance in nonclinical safety assessment and the unique attributes of ONTs, the forum discussed case studies, consensus approaches, and areas needing further development to optimize DART strategies. This report covers the workshop proceedings, highlighting methods to achieve a robust DART assessment for ONTs. It includes case studies that described strategies for dose level selection, dosing frequency, species selection, and alternative animal model approaches. Topics also cover surrogate ONT use, exposure of the placenta and embryo/fetal compartment, and weight of evidence approaches. A goal of these workshop proceedings is to describe example approaches to hopefully inform the DART strategy expectations in the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidance currently under development for nonclinical safety assessment of ONTs.</p>\",\"PeriodicalId\":19412,\"journal\":{\"name\":\"Nucleic acid therapeutics\",\"volume\":\" \",\"pages\":\"93-113\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nucleic acid therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1089/nat.2025.0013\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nucleic acid therapeutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/nat.2025.0013","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/30 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

2023年的研讨会汇集了参与寡核苷酸(ONT)治疗药物开发和安全性评估的利益相关者。目的是讨论加强ONTs发育和生殖毒性(DART)评估的潜在策略和机会。该研讨会是及时的,汇集了监管机构、行业代表、顾问和合同研究组织合作伙伴,他们对正在进行的ONTs非临床安全评估国际统一指南的发展感兴趣。鉴于DART在非临床安全性评估中的重要性和ont的独特属性,论坛讨论了案例研究、共识方法和需要进一步发展的领域,以优化DART策略。本报告涵盖了研讨会会议记录,重点介绍了为ont实现可靠的DART评估的方法。它包括案例研究,描述了剂量水平选择、给药频率、物种选择和替代动物模型方法的策略。主题还包括代理ONT的使用,胎盘和胚胎/胎儿室的暴露,以及证据权重方法。这些研讨会会议记录的一个目标是描述示例方法,希望在目前正在开发的用于ONTs非临床安全性评估的国际人用药品技术要求协调委员会指南中告知DART战略期望。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Developmental and Reproductive Toxicity Testing Strategies for Oligonucleotides: A Workshop Proceedings.

A 2023 workshop brought together stakeholders involved in the development and safety assessment of oligonucleotide (ONT) therapeutics. The purpose was to discuss potential strategies and opportunities for enhancing developmental and reproductive toxicity (DART) assessment of ONTs. The workshop was timely, bringing together regulators, industry representatives, consultants, and contract research organization partners interested in the ongoing development of internationally harmonized guidance for nonclinical safety assessment of ONTs. Given DART's importance in nonclinical safety assessment and the unique attributes of ONTs, the forum discussed case studies, consensus approaches, and areas needing further development to optimize DART strategies. This report covers the workshop proceedings, highlighting methods to achieve a robust DART assessment for ONTs. It includes case studies that described strategies for dose level selection, dosing frequency, species selection, and alternative animal model approaches. Topics also cover surrogate ONT use, exposure of the placenta and embryo/fetal compartment, and weight of evidence approaches. A goal of these workshop proceedings is to describe example approaches to hopefully inform the DART strategy expectations in the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidance currently under development for nonclinical safety assessment of ONTs.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Nucleic acid therapeutics
Nucleic acid therapeutics BIOCHEMISTRY & MOLECULAR BIOLOGY-CHEMISTRY, MEDICINAL
CiteScore
7.60
自引率
7.50%
发文量
47
审稿时长
>12 weeks
期刊介绍: Nucleic Acid Therapeutics is the leading journal in its field focusing on cutting-edge basic research, therapeutic applications, and drug development using nucleic acids or related compounds to alter gene expression. The Journal examines many new approaches for using nucleic acids as therapeutic agents or in modifying nucleic acids for therapeutic purposes including: oligonucleotides, gene modification, aptamers, RNA nanoparticles, and ribozymes.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信