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Chinese scientists attempt to cure HIV of one person with Crispra



Until now, scientists had hoped only to control the insidious disease through drugs such as PrEP that reduced transmission or antiretroviral treatments that maintained patients' immune systems. A Berlin patient made them believe that total destruction of viruses was actually possible.

Its story galvanizes laboratories and companies around the world that do it with the help of genetic engineering. In 2009, California-based Sangamo Therapeutics launched the first human trials to edit a gene for treating HIV using an older technology called zinc-finger nucleases. These attempts to edit human T cells have led to limited success.

A better approach, according to many, is to edit the cells that make T cells (and all other blood and immune cells) deep into human bones instead. Known as hematopoietic stem cells, they are more editable and require more risk and discomfort to deliver. But if you succeed, you can provide the patient with a lifelong supply of HIV-immune blood and immune cells. This seems to be offered by Crispr.

The Chinese research team, which conducted the most recent study, previously transplanted Crispr mutated human cells of CCR5 into mice, making them resistant to HIV infection. In the spring of 201

7, they registered a small human process that will take place at the 307 Beijing People's Liberation Army Hospital. So far, researchers have enrolled and treated only one patient, according to Hongkong Day, director of the Beijing University Stem Cell Research Center and one of the study's co-authors. But Deng expects the test to expand as their technique improves.

To edit the donor stem cells, Deng's team placed them in a machine that applied a slight electric shock. This allows the components of Crispr – the DNA cutting enzyme and GPS guides that tell it where to cut – to slip through the cell membrane and work. This approach minimizes potential errors known as non-target effects, since Crispr is only in the cells for a short period of time, meaning that they are unlikely to cheat and break DNA that is not supposed to. But it also means that not all cells are editable.

In an ideal world, both copies of the CCR5 gene would be truncated in all 163 million or so stem cells that are isolated from the donor's bone marrow. This will replicate what the Berlin patient received from his donor. What the researchers got instead was much lower. After transplantation, only between 5.2 and 8.3 percent of the patient's bone marrow cells carry at least one copy of the CCR5 revision. (The study authors did not report how many cells had both copies against a single copy.)

This number remained more or less stable during the 19 months that researchers have so far tracked the patient. But the more telling question is whether the T cells in the patient's blood also retain editing. In the specific type of T cells that HIV uses to infiltrate the immune system, the broken version of CCR5 is present in only about 2% of them.

"This leaves a lot of room for improvement," says Paula Cannon, a molecular microbiologist who studies HIV and gene editing at the University of Southern California at Keck Medical School. "At these levels, cells are not expected to have much effect against the virus."

Another clinical trial, led by the City of Hope of Los Angeles, examines the use of zinc-finger nucleases to edit the hematopoietic stem cells of HIV-positive people, with a less aggressive step to cleanse the bone marrow, which you could call it chemo-lit. So far, six patients have been treated, and again in 500 days only about 2 to 4 percent of the cells have carried the mutation, according to data presented at the HIV / AIDS conference last month in Seattle.


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