CRISPR kills HIV and eats Zika ‘like Pac-man’. Its next target? Cancer
Researchers paired proteins with a process that amplifies RNA which could be used to detect cancer cells
HIV has no cure. It’s not quite the implacable scourge it was throughout the 1980s and 1990s, thanks to education, prophylactics, and drugs like PrEP. But still, no cure.
Part of the problem is HIV’s ability to squirrel itself away inside a cell’s DNA – including the DNA of the immune cells that are supposed to be killing it. The same ability, though, could be HIV’s undoing. All because of CRISPR. You know, CRIPSR: the gene-editing technique that got everyone really excited, then really sceptical, and now cautiously optimistic about curing a bunch of intractable diseases.
Last week, a group of biologists published research detailing how they hid an anti-HIV CRISPR system inside another type of virus capable of sneaking past a host’s immune system. What’s more, the virus replicated and snipped HIV from infected cells along the way. At this stage, it works in mice and rats, not people. But as a proof of concept, it means similar systems could be developed to fight a huge range of diseases — herpes, cystic fibrosis, and all sorts of cancers.
Those diseases are all treatable, to varying degrees. But the problem with treatments is you have to keep doing them in order for them to work. “The current anti-retroviral therapy for HIV is very successful in suppressing replication of the virus,” says Kamel Khalili, a neurovirologist at Temple University in Philadelphia and lead author of the recent research, published in Molecular Therapy. “But that does not eliminate the copies of the virus that have been integrated into the gene, so any time the patient doesn’t take their medication the virus can rebound.” Plus treatments can — and often do — fail.
Gene therapy has promised to revolutionise medicine since the 1970s, when a pair of researchers introduced the concept of using viruses to replace bad DNA with good DNA. The first working model was tested on mice in the 1980s, and by the 1990s researchers were using gene therapies — with limited success — to treat immune and nutrition deficiencies. Then, in 1999, a patient in a University of Pennsylvania gene therapy trial named Jesse Gelsinger died from complications. The tragedy temporarily skid-stopped the whole field. Gene therapy had been steadily getting its groove back, but the 2012 discovery that CRISPR could make easy, and accurate, cuts on human genes, added more vigor.
CRISPR as an agent for curing HIV has its own problems. For one, it has to be able to snip away the HIV from an infected cell without damaging any of the surrounding DNA. HIV mutates and evolves, so Khalili and his co-authors couldn’t just program their CRISPR system with a single genetic mugshot. Instead, they had to target enough unchanging sections that were also critical to the virus’ survival.
Their next challenge was delivering the system to a critical mass of infected cells. First, you have to get it past the immune system – which is programmed to attack any foreign object entering the body. They did this by packing their CRISPR system inside another type of virus called AAV (short for adeno associated virus). “AAVs are a very small helper virus, they can’t actually replicate in a cell on their own unless they have another virus there to help it along,” says Keith Jerome, a microbiologist at the Fred Hutchinson Cancer Research Centre in Seattle. “The great thing about AAVs is they cause essentially no immune system response in humans.” The death of Gelsinger in 1999 was due to the fact his therapy involved corrected genes and an actual adenovirus (a weakened cold virus) which acted like a vector, as opposed an AAV. AAVs are currently being used as vectors in clinical trials for haemophilia A and B with minimal side effects.
But still, doctors hoping to prescribe AAV-based gene therapy have to be aware of patients’ prior exposure.
In order to get approved for human use, this type of CRISPR-borne cure would have to be both safe and effective. This study got part of the way but was going strictly for efficacy: Does this work? Khalili and his co-authors treated mice and rat model with strains of HIV that were latent; hiding away in cellular DNA—and others where the HIV was actively replicating. Then they used it on mice grafted with human cells. In all three cases, HIV rates went down significantly.