Researchers were able to replicate the functional cure of HIV that was seen in the "Berlin patient" in a mouse model, according to a study conducted at the University of California, Davis.
The study, which was published in the journal Stem Cells, genetically engineered human stem cells to be HIV resistant, purified them and implanted the resulting cells in mice. After being infected with two different strains of HIV, these mice maintained normal CD4+ cell counts and tested negative for HIV in their blood. Six months later the mice continued to have an apparently normal immune system, without any signs of toxicity or tumors.
Previous attempts at HIV gene therapy had not been very efficacious because only a small proportion of the transplanted stem cells were of the HIV-resistant variety. By contrast, this study used a pre-selective anti-HIV lentiviral vector based on human CD25 cells to purify and enrich the genetically altered stem cells.
The process resulted in an average 94.2% (range: 89.6% to 98.3%) of the altered cells expressing anti-HIV genes, compared to the approximately 17.5% expressed in previous HIV gene therapy work. Thus almost all the genetically altered stem cells transduced into the mice were HIV resistant, allowing for the replacement of practically all of the animals' immune systems.
"This level of protected cells is significantly better than initial transduction efficiencies which would have been used for patient transplants," the study authors noted.
By inserting three different HIV-resistant genes, researchers produced stem cells that protect the immune system against many mutations of the virus. Each of the genes confers resistance to a different HIV replication strategy, inhibiting various stages of the HIV life cycle: exposure of the virus' genetic material inside a cell, attachment to target cells, and functioning of a specific protein required by HIV.
All three genes had been used in previous studies, but without the pre-selective vector. The combination of the modified genes and the newly developed vector "brings us closer to mimicking the results observed with the 'Berlin patient'," the study authors concluded.
"We are now poised to evaluate the effectiveness of this therapy in human clinical trials," said lead researcher Joseph Anderson, Ph.D. Trials were recently approved by the U.S. Food and Drug Administration that will use stem cells retrieved from a patient's own bone marrow to avoid the common risk of the body rejecting the transplanted cells.