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Stanford University School of Medicine

A step closer to gene therapy for sickle cell disease

porteus_sickleIn the 1980s, molecular biologists conceived the idea of gene therapy, in which a genetic disease might be cured by replacing the mutated disease-causing gene variant with a functioning version of the same gene.

Exactly how to do that though wasn't obvious. The first challenge was precisely replacing one gene variant with another. Another challenge was replacing all the cells in the body carrying the bad gene -- or at least as many cells as would cure symptoms of the disease. A third challenge was ensuring the healthy cells displaced the disease-causing cells for a long time, even permanently. And a fourth was to meet the first three challenges without causing harmful side effects.

Needless to say, overcoming those challenges is exceedingly challenging. Researchers have been able to genetically modify cells for decades, but the invention of the CRISPR gene editing tool a few years ago transformed the field, enabling rapid, accurate gene editing. It's a technology so hot it has its own television show.

Now that researchers also have the ability to collect adult stem cells from individual patients, modify them and reintroduce them to the same person, the promise of gene therapy has come to seem -- to many -- nearly within reach.

Diseases of the blood are among the most amenable to gene therapy because circulating blood cells are easy to retrieve and reintroduce to the body. So it's no surprise that sickle cell disease, caused by a single mutation in the gene that makes the oxygen-carrying molecule hemoglobin, has become a favorite target for gene therapy techniques.

A multitude of such approaches have been tried against sickle cell disease. But now a team of researchers at Stanford has used CRISPR to repair the human stem cells that make sickle cell red blood cells, publishing their work in Nature.

As senior author Matthew Porteus, MD, PhD, a stem cell transplanation specialist, told me for my news release:

What we've finally shown is that we can do it... It's not just on the chalkboard. We can take stem cells from a patient and correct the mutation and show that those stem cells turn into red blood cells that no longer make sickled hemoglobin.

The Porteus team injected the corrected stem cells into mice, and the mended cells successfully took up residence in the bone marrow.

But doing the same in humans means phase I clinical trials that evaluate safety and phase II clinical trials that evaluate effectiveness. All of that will take time, so sickle cell patients and familes will need to be patient.

A note on the research: Porteus has equity interest in CRISPR Therapeutics, which recently launched an initial public offering.

Previously: CRISPR marches forward: Stanford scientists optimize use in human blood cells"It's not just science fiction anymore": Childx speakers talk stem cell and gene therapy and Experimental bone marrow treatment appears to reverse sickle cell disease
Photo by Decade3D - Anatomy Online/Shutterstock

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