Gene editing tool can write HIV out of the picture
Think of this blend, the wonder stem cells from 2012 which won a discover Nobel prize and a new method that has opened up a new era of genetic engineering. What you will find is from those two components, that you might have found yourself a tool to cure HIV.
Well this is the hope of researchers that are being led by Yuet Kan of the University of California. They have also proved the basic principle, altering the genome of induced pluripotent stem cells to give them a rare natural mutation that allows certain people to resist HIV.
This work relies heavily on genome editing, snipping out a particular DNA sequence and replacing it with another. This process is more precise than traditional forms of genetic engineering, in which sequences are added to the genome at random locations.
The CRISPR-Cas9 system has been used to alter stem cells. The CRISPR-Cas9 system is a super efficient method of genome editing based on a ancient bacterial immune system. The system takes different parts of the DNA from invading invading infections and splices them into the cell’s own DNA. Where it posts it as a warning sign allowing the infection to recognised and attacked in the future.
In the world about 1% of people that are of European descent are resistant to HIV as they carry two copies of a mutation in the gene for a protein called CCR5. To become infected by the HIV virus it must lock onto the CCR5 protein before it can invade white blood cells however the mutations prevent it from doing so.
Timothy Ray Brown was famously cured of HIV after having a bone marrow transplant from a naturally HIV resistant person. Kan’s goal is to achieve the same result without the need to find compatible HIV-resistant bone marrow donors, who are in very short supply.
IPSCs are easily made from a person’s cells, from they have the potential to grow into any type of cell in the body. If the two copies of the protective mutation could be given to an iPSCs, it should in theory be possible to make personalised versions of the therapy that cleared HIV from Brown’s body. The team from California have shown that CRISPR-Cas9 can efficiently make the necessary genome edit and as expected the white blood cells grown from these altered stem cells were resistant to HIV when tested.
“It’s a really fantastic application of the tool,” says Philip Gregory, chief scientific officer with Sangamo BioSciences of Richmond, California. However, he warns that there is a long way to go before it can be turned into a practical therapy.
Kan has yet to grow the iPSCs into the specific type of white blood cells, which are called CD4+T cells that are ravaged by HIV. Kan instead plans to do is turn the iPSCs into blood forming stem cells. Which when they have been transplanted into the body would form cell types found in the blood “One of the problems is converting iPSCs into a type of cell that is transplantable,” says Kan. “It is a big hurdle.”
This isn’t the only hurdle as regulators will also need to be convinced that cells have been subjected to extensive genetic manipulation, both for the creation of the iPSCs and to give them the protective mutation are safe.
Currently Sangamo is already testing s therapy that uses an older genome editing technique to disrupt CCR5 in patients so that HIV is locked out. In an initial trial involving a handful of people with HIV, levels of the virus circulating in the blood decreased and became non detectable in one person.
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