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. 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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.
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.