This strategy, Dornbusch says, will save patients from serious side effects or “untargeted” edits — unintentional cuts elsewhere in the genome that can cause problems like cancer.
The regions targeted by the company’s Crispr therapy are also in a part of the genome that tends to stay the same even as HIV progresses. That’s important because viruses mutate quickly and researchers don’t want a target to move.
This isn’t the first time scientists have tried to use gene editing in the hope of curing people with HIV, but other efforts have focused on a protective mutation in a gene called CCR5. In the 1990s, scientists discovered that people with this natural mutation do not become infected with HIV when exposed to it. The mutation — called delta 32 — prevents the virus’s ability to get inside immune cells. In 2009, California-based Sangamo Therapeutics used an older editing technology called zinc finger nucleases to add that protective mutation to a patient’s T cells – a key part of the immune system. . Those tests were there limited success.
In 2017, Chinese scientists combined Crispr with a bone marrow transplant in one trying to save a patient with HIV and leukemia. In a typical transplant, donor stem cells are delivered to the recipient to replace their cancerous blood cells. These cells go on to form new, healthy blood cells. To solve a patient’s HIV problem, researchers edited donor stem cells with Crispr to neutralize CCR5. But after the transplant, only a small percentage of the patient’s bone marrow cells were edited as desired.
Then, in 2018, Chinese scientist He Jiankui used Crispr to edit CCR5 mutated into the genome of twin girls to make them resistant to HIV. Filled with moral violationtest is widely condemned by scientists. His research was suspended by the Chinese government and he was sentenced to three years in prison. While the twins were born healthy, only some of their cells were successfully edited, meaning the girls may not in fact be immune to HIV.
As of 2022, two people now cured of HIV after receiving bone marrow transplants from donors with CCR5. Called the Berlin patient and London patient, both had cancer and received a transplant to treat their disease. But these transplants aren’t a viable option for most people – they’re risky, and donors with the delta 32 mutation are scarce. But the third person was claimed to have cured HIV earlier this year after she received a new type of transplant involving cord blood.
The final Exclusion Trial will enroll nine participants and test three doses to determine which is most effective. Investigators will measure each person’s viral load and CD4 count before receiving therapy and after they stop taking their antiretroviral medication. The ultimate goal is to reduce the viral load to an undetectable level – that is, less than 200 HIV copies per milliliter of blood. At this level, HIV cannot be sexually transmitted.
The challenge for Excision will be to get Crispr to enough cells to bring HIV down to undetectable levels. The company is using a virus that has been engineered to deliver gene-editing components to a patient’s HIV-infected CD4 cells. But so far, there is little human data on how well Crispr works when it is administered directly into the body. “There’s a chance that you’ll get the virus down to such a low level that if a person’s immune system is intact, they can keep the virus at bay so that they don’t have to be treated with antibiotics,” said Rowena Johnston, associate dean of the department. viruses too,” said Rowena Johnston, research vice president of amfAR, Foundation for AIDS.
And while these drugs are very effective, says Johnston, many people still want to be completely virus-free. A single infusion of Crispr – if it works – eliminates the need for a daily pill. “People living with HIV still live with a lot of internal stigma and shame,” she said. “I think a cure is a much better problem solver than lifelong therapy, no matter how easy that therapy becomes.”
