Comparative Evaluation of the Activity of Various Lentiviral Vectors Containing Three Anti-HIV Genes.
Olga Vladimirovna OrlovaDina Viktorovna GlazkovaRamil Rafailovich MintaevGalina Mikhailovna TsyganovaFelix Anatolevich UrusovGerman Alexandrovich ShipulinElena Vladimirovna BogoslovskayaPublished in: Microorganisms (2023)
A promising direction in the treatment of HIV infection is a gene therapy approach based on the insertion of antiviral genes aimed at inhibiting HIV replication into the genome of host cells. We obtained six constructs of lentiviral vectors with different arrangements of three antiviral genes: microRNAs against the CCR5 gene, the gene encoding the C-peptide, and the gene encoding the modified human TRIM5a protein. We found that despite containing the same genes, these vectors were produced at different titers and had different effects on cell viability, transduction efficiency, and expression stability. Comparative evaluation of the antiviral activity of three of the six developed vectors that showed stable expression was carried out using the continuous SupT1 lymphocytic cell line. All of the vectors protected cells from HIV infection: the viral load was several orders of magnitude lower than in control cells, and with one vector, complete cessation of virus growth in modified cells was achieved.
Keyphrases
- gene therapy
- genome wide
- genome wide identification
- induced apoptosis
- antiretroviral therapy
- cell cycle arrest
- hiv infected
- dna methylation
- poor prognosis
- hiv positive
- human immunodeficiency virus
- signaling pathway
- genome wide analysis
- hepatitis c virus
- endoplasmic reticulum stress
- bioinformatics analysis
- endothelial cells
- copy number
- cell death
- transcription factor
- binding protein
- immune response
- oxidative stress
- regulatory t cells
- protein protein
- induced pluripotent stem cells
- smoking cessation
- combination therapy
- amino acid