A Future without Illness: Gene Editing with CRISPR

When a baby is born & if their immune system is compromised or there is a tiny mistake in the DNA sequence along the X chromosome, the neutrophils in the baby’s blood will be incapacitated.

Adapted from Kendall K. Morgan in Genome, Summer 2017

Neutrophils are an essential component in the body’s first line of defense against infectious bacteria and fungi. This would lead to a rare immune disorder called chronic granulomatous disease (CGD). Such babies would have to live & survive on antibiotic & antifungal medications, countless CT scans and frequent, sometimes prolonged hospital stays to manage life threatening infections.

Suk See De Ravin from the National Institute of Allergy & Infectious Diseases (NIAID), a division of NIH in Bethesda, Maryland, strongly advises such patients to make lifestyle changes. “They must avoid situations where there would be increased risk of infection. Playing in the dirt, raking up leaves etc. would be all a no-no activity. The reason these activities are off limits for kids & adults with CGD is because of the molds and mold spores that lurk in many places, both indoors and out. Most of us can and do breathe those spores into our lungs daily without issue. But in people with CGD the risk of developing a life threatening fungal infection is very high.

Research on CGD is underway at NIAID in Bethesda. In the 70’s CGD research was focused on learning how to manage the disease, using aggressive anti-microbial treatments to combat the inevitable infections and, in some cases, invasive surgeries to remove infected masses of tissues. But, now at NIAID researchers are using gene-editing tool called CRISPR – Cas9. The CRISPR tool includes a cutting enzyme, often likened to a pair of scissors, which researchers have borrowed from bacteria. A key feature of these molecular scissors is that they can be readily programmed to cut the genome very precisely with the addition of short snippets of guide RNA that match the gene (or genes) of interest.

CRISPR is considered a biological revolution. If it can be delivered safely and successfully, it would have clear advantages. Malech, NIAID, in Science Translational Medicine says “Nature has devised the system to work in an ideal way. What gene editing with CRISPR does when it repairs a mutation is essentially to bring the cell back to that ideal”. In a clinical trial last year, Chinese scientists injected the first patient with T cells they’d edited with CRISPR. While the results of the trial aren’t out yet, the cells were programmed to more effectively fight against an aggressive form of lung cancer.

Carl June, at the University of Pennsylvania in Philadelphia has pioneered an approach to modifying T cells to attack cancer using a variety of tools. June and his group anticipate launching what may be the first trial of CRISPR-edited T cells in the US, with backing from internet billionaire Sean Parker, a creator of Napster and the first president of Facebook.

The conditions for which CRISPR has the potential to make an impact in the near term include sickle cell disease, hemophilia, HIV, and Duchenne muscular dystrophy. Gersbach of Duke University says that T-cells from the blood are easily modifiable using CRISPR because they can be taken out of the body, edited in the lab, and then returned to the body via infusion. CRISPR technology is however not limited to blood cells. The company Editas is expected to launch a clinical trial using CRISPR to edit rare form of blindness out of the retina. Many also hope that CRISPR can one day be used to eradicate HIV. Recently, researchers at Temple University in Philadelphia successfully removed the HIV virus from infected cells in mice.

As with any procedure there may be risks. CRISPR could create nicks in parts of the DNA where it shouldn’t. Scientists will have to minimize the risks of CRISPR as best as they can. Then, as with any other treatment, doctors and patients will have to weigh the risks and benefits of CRISPR as demonstrated in clinical trials against the other alternatives.

CRISPR is a breakthrough for more than 200 CGD affected families. Hopefully it will give them a fully functional immune system and a future without illness.

ScienceBuzz Admin

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A Future without Illness: Gene Editing with CRISPR

When a baby is born & if their immune system is compromised or there is a tiny mistake in the DNA sequence along the X chromosome, the neutrophils in the baby’s blood will be incapacitated.

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