General genomic DNA of transduced cells

General genomic DNA of transduced cells refers to the host cell's chromosomal DNA that has been modified by the introduction of foreign genetic material, typically via viral vectors or gene-editing tools (Nature Education, 2014). In the context of gene therapy, this substrate represents the site of integration or modification where a therapeutic transgene is placed or an endogenous gene is corrected (NIH/NHGRI, 2020). While not a traditional drug target like a receptor or enzyme, the genomic DNA is the fundamental substrate for advanced therapy medicinal products (ATMPs). The interaction involves the stable or transient presence of new genetic sequences that aim to treat diseases by producing missing proteins or silencing harmful ones. However, non-specific or poorly controlled modification of genomic DNA carries significant risks, including insertional mutagenesis, which can lead to oncogenesis if the transgene integrates near a proto-oncogene (FDA Guidance for Industry, 2022). Monitoring the integrity and specific location of these modifications, such as through vector copy number (VCN) and integration site analysis (ISA), is a critical component of safety and efficacy assessments in cell and gene therapy development. This 'target' is central to the development of CAR-T cell therapies, hematopoietic stem cell gene therapies, and in vivo gene editing applications.

Other names

Host cell genomeTransduced genomeProviral DNAIntegrated transgene DNAHost chromosomal DNA

Modification of the host genome through stable integration of a transgene, transient expression of genetic material, or precise sequence editing to restore, supplement, or silence cellular functions.