Scientists eliminate HIV infection in 'humanised' mice
Scientists have successfully removed HIV DNA from the genomes of 'humanised' mice, using CRISPR/Cas9 gene-editing tool, a step which in the future may help eliminate the virus in humans. The researchers were able to genetically inactivate the human immunodeficiency virus type-1 (HIV-1) in mice, that had been injected with human genes and cells.
New York, May 2 (PTI) Scientists have successfully removed HIV DNA from the genomes of animals - including a humanised mice - using a powerful gene-editing tool, an advance that may help eliminate the virus in humans in future. The team is the first to demonstrate that human immunodeficiency virus type 1 (HIV-1) replication can be completely shut down and the virus eliminated from infected cells in animals with a powerful gene editing technology known as CRISPR/Cas9. Researchers, including those from Temple University in the US, build on their previous study in which they used transgenic rat and mouse models with HIV-1 DNA incorporated into the genome of every tissue of the animals bodies. They demonstrated that their strategy could delete the targeted fragments of HIV-1 from the genome in most tissues in the experimental animals. The researchers genetically inactivated HIV-1 in transgenic mice, reducing the RNA expression of viral genes by roughly 60 to 95 per cent. They then tested their system in mice acutely infected with EcoHIV, the mouse equivalent of human HIV-1. In the third animal model, latent HIV-1 infection was recapitulated in humanised mice engrafted with human immune cells, including T cells, followed by HIV-1 infection. In all three animal models, the researchers utilised a recombinant adeno-associated viral (rAAV) vector delivery system based on a subtype known as AAV-DJ/8. "The AAV-DJ/8 subtype combines multiple serotypes, giving us a broader range of cell targets for the delivery of our CRISPR/Cas9 system," said Wenhui Hu, associate professor at Temple University. Researchers also re-engineered their previous gene editing apparatus to carry a set of four guide RNAs, all designed to efficiently excise integrated HIV-1 DNA from the host cell genome and avoid potential HIV-1 mutational escape. 