Risks of replication-competent retro/lentivirus from associated vector systems: Is it time for a roadmap toward reduced testing?

ABSTRACT: The development of retroviral and lentiviral vectors (RV/LVs) has culminated in third-generation vector systems with excellent safety profiles. However, there has been no significant (re)assessment of RCR/RCL formation risk within RV/LV systems regarding the underlying molecular recombination events, despite updated guidance for RCR/RCL assay development/testing issued by the key regulatory agencies. This review reflects on genuine RCRs generated in early vector systems that drove the development of the common safety features of all third-generation systems. We then present a "minimal-path" model for RCL formation within four-component LV systems, which draws on published recombination rates between plasmid DNA in cell lines and retrovirus genomic RNA during reverse transcription. This mod

SUBMITTER: Farley D 

PROVIDER: S-EPMC12552945 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature