Gene therapy in the treatment of HIV
Scientists are testing 2 approaches
Tatiana Ten, Life4me+
Clinical trials of new approaches to gene therapy can pave the way to a functional cure or long-term remission of HIV. American Gene Technologies is testing genetically modified HIV-specific CD4 T cells resistant to virus penetration, and Excision BioTherapeutics is developing a method for removing HIV DNA from the chromosomes of infected cells. A review of the research is published in the journal POZ.
American gene technology: AGT103-T
The AGT Phase I RePAIR trial is exploring a "one-time gene and cell treatment" that could allow people living with HIV to opt out of ARV therapy without fear of developing AIDS or transmitting the virus to others.
The experimental therapy, called AGT103-T, includes genetically modified CD4 T cells capable of resisting HIV. First, a sample of peripheral blood cells is taken from the patient and CD4 cells that recognize the HIV Gag protein are selected. Then a gene is inserted into the cell that disables the CCR5 receptors that HIV uses to enter the cells. Eventually, the modified CD4 is returned to the body.
According to the data, the first clinical trial of AGT103-T is successful. After evaluating the interim results of the first 3 participants, the independent safety board found no serious side effects. It is expected that 2 more patients will receive treatment this month.
"One patient may be lucky. Two can be very lucky. Three is a trend, so the data security and monitoring board has decided that the trial can proceed at a faster pace from now on," said AGT CEO Jeff Galvin.
The real test of a functional cure is stopping taking antiretroviral drugs to see if the viral load will recover. The first participants will begin a carefully controlled interruption of treatment in early 2022, the researchers report.
"After 3 more participants undergo treatment in November and December, we will be able to start studying the data on effectiveness. We expect to see objective markers in blood tests of treated participants by the end of the year and hope that by the summer of next year we will have a functionally recovered patient," Galvin said.
Excision Biotherapy: EBT-101
Excision BioTherapeutics takes a different approach, using gene therapy to deactivate HIV genetic codes in infected cells, thereby stopping the production of a new virus.
EBT-101 uses a CRISPR-based technology for cutting out viral genes. The system uses RNA templates to localize HIV proviral DNA in CD4 cell chromosomes and cuts this DNA using a nuclease enzyme. Then the "cell repair mechanism" connects the DNA sections.
"If you just make one incision, the virus can mutate around it. We are making several incisions to deactivate the viral genome," Excision CEO Daniel Dornbush said.
EBT-101 is administered as a single intravenous infusion. Three months after administration, the study participants will begin a controlled break in treatment with antiretroviral drugs to see how gene therapy affects the development of the virus.
In September, the FDA gave the company the go-ahead to start the first phase of EBT-101 trials.
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