Improving the Assessment of Risk Factors Relevant to Potential Carcinogenicity of Gene Therapies: A Consensus Article.
Jan C KlapwijkAlberto Del Rio EspinolaSilvana LibertiniPhilippe CollinMick D FellowsSusan JoblingAnthony M LynchHansJoerg MartusCatherine VickersAndreas ZellerLuca BiascoMartijn H BrugmanFrederic D BushmannToni CathomenHildegrund C J ErtlRichard GabrielGuangping GaoJulie K JadlowskyIan KimberThomas A LanzBruce L LevineKenneth P MicklethwaiteMasafumi OnoderaDaniella M PizzurroSimon ReedMichael RotheDenise E SabatinoJesse J SalkAxel SchambachMichael ThemisJing YuanPublished in: Human gene therapy (2024)
Regulators and industry are actively seeking improvements and alternatives to current models and approaches to evaluate potential carcinogenicity of gene therapies (GTs). A meeting of invited experts was organized by NC3Rs/UKEMS (London, March 2023) to discuss this topic. This article describes the consensus reached among delegates on the definition of vector genotoxicity, sources of uncertainty, suitable toxicological endpoints for genotoxic assessment of GTs, and future research needs. The collected recommendations should inform the further development of regulatory guidelines for the nonclinical toxicological assessment of GT products.