Stable integration into host genome is a feature of:
Lentiviral vectors originating from HIV-1 carry two copies ssRNA genome 9 kb encapsidated with reverse transcriptase, integrase, nucleocapsid. Entry mediated by VSV-G pseudotyping binding LDL receptor ubiquitous, membrane fusion releasing core into cytoplasm where reverse transcriptase synthesizes ds cDNA via tRNA lys3 primer and strand transfer forming preintegration complex containing integrase, matrix p17, Vpr, host LEDGF p75 tethering factor. Complex traverses intact nuclear pore via importin alpha/beta pathway recognizing nuclear localization signals allowing transduction nondividing cells such as neurons and quiescent HSC unlike gamma retroviruses dependent on mitotic envelope breakdown. Integrase catalyzes 3 prime processing removing GT dinucleotides and strand transfer inserting provirus preferentially into active transcription units enriched H3K36 trimethylation marked by LEDGF reader ensuring expression. Self-inactivating design deletes U3 enhancer promoter in LTR abolishing LTR transcriptional activity reducing oncogenic transactivation risk. Integrated provirus replicates with host chromosomes providing stable long-term expression utilized in ex vivo hematopoietic correction and CAR-T manufacturing where durability essential despite low insertional risk.
Ref: Danaher Lentiviral Integration Mechanism; PMC Lentiviral Delivery CRISPR Review; NIH AAV vs Lentivirus Integration Safety.