With so much discussion around Limits and AI calculations, I want to debate for a moment to share information about ‘Duplex Sequencing’. After the recent safety discussion at the Hesi/FDA meeting, I went down a rabbit hole to understand some of the proposed assays and testing that can be used to evaluate the safety or mutagenicity potential in Nitrosamines Impurities.
Duplex Sequencing - I would like to share couple peer-reviewd articles that provide a perspective about duplex sequencing and how this can be used to assess mutaginicity.
Does anyone has experience performing duplex sequencing (DS) methodology in wild-type rodent tissues, without the need for transgenic animals? Are there any reliable CRO’s for performing DS analyses?
I understand one of the beneficts of DS is that you do not need transgenic animals + the cost compared to a TGRA. If I am not mistaken DS is a propietary methodology, at least part of the materials.
The only caveat, is that there is no OECD guideline for it and that may take years. Therefore, to avoid heterogenicity, a common “procedure” done by sponsors should be available first.
I believe DS is just one of the next-generation sequencing method and TwinStrand Biosciences actually developed a DS-based mutagenesis assay. However, except for the TwinStrand I could not come across any other CRO performing duplex sequencing for which I believe is a promising tool for cost-effective, accurate and time efficient method.
