Host genomic DNA at lentiviral integration sites

Host genomic DNA at lentiviral integration sites refers to the specific chromosomal loci where lentiviral genetic material is covalently inserted into the host genome. This process is mediated by the viral integrase enzyme, which shows a preference for integrating into transcriptionally active regions of the DNA (Schröder et al., 2002, Cell). In the field of gene therapy, these sites are critical for the long-term expression of therapeutic transgenes in cells such as CAR-T lymphocytes or hematopoietic stem cells (Milone & O'Doherty, 2018, Leukemia). However, the semi-random nature of integration carries a risk of insertional mutagenesis, potentially leading to the activation of proto-oncogenes or the disruption of tumor suppressor genes (David & Doherty, 2017, Gene Therapy). Consequently, monitoring these integration sites through high-throughput sequencing is a standard safety requirement to detect clonal dominance or genotoxic events in patients (Schmidt et al., 2007, Nature Methods). In the context of HIV, these integration sites harbor the latent proviral reservoir, which remains the primary obstacle to a functional cure (Siliciano & Greene, 2011, Cold Spring Harbor Perspectives in Medicine).

Other names

Lentiviral integration sitesProviral integration sitesGenomic integration sitesHIV-1 integration sitesHIV-1 proviral DNA

Lentiviral vectors utilize the viral integrase enzyme to catalyze the covalent insertion of the vector genome into the host cell chromosomal DNA, typically within actively transcribed regions (Bushman, 2003, Nature Reviews Microbiology). This integration ensures that the therapeutic gene is permanently incorporated into the host cell genome and passed on to all progeny cells (Milone & O'Doherty, 2018, Leukemia).