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Gene Editing of Stem Cells Hastened

A new technique has demonstrated how genetically repaired stem cells can be derived from patient skin cells in as little as 2 weeks, compared with conventional multi-step approaches that take more than 3 months.

The key to the advance, published in Stem Cell Reports (tinyurl.com/plhzruf), is to combine two essential steps when preparing cells for potential therapy. First, adult cells must be reprogrammed to an embryonic cell-like state in order to be differentiated into the cells of therapeutic interest. The cells then need to undergo a sophisticated gene-editing process to correct the disease-causing mutation.

Dr Sara Howden of the Murdoch Childrens Research Institute successfully combined these two steps in skin cells derived from an adult patient with retinal degeneration as well as an infant patient with severe immunodeficiency. “The method developed in our study could potentially advance transplant medicine by making gene-corrected cells available to patients in a much more timely manner, and at a lower cost,” Howden says.

Howden says the faster process, using Cas9/CRISPR technology, also means the cell culture period is greatly reduced, potentially minimising the risks associated with culturing cells outside of the human body, such as genome instability or other epigenetic changes.

Induced pluripotent cells (iPS cells) hold great promise for medical research because they can essentially be derived from any individual and are capable of becoming any of the 220 types of cells in the human body. The ability to efficiently and precisely modify the DNA in these cells offers enormous potential for the development of personalised stem cell therapies that benefit people with many different types of genetic disorders.

Howden says one potential next step is to adapt the protocol to work with blood samples. Not only is a blood sample less invasive than a skin biopsy, it also could further reduce the time to obtain genetically repaired iPS cells. Skin cells need to be expanded for several weeks before initiating reprogramming.

Howden says this “fast-tracked process” could be most influential in cases where urgent medical intervention is needed. One example is severe combined immunodeficiency, where children typically die within the first few years of life.

However, Howden says that scientists still need to derive a long-term source of blood cells from pluripotent stem cells before such treatments are viable.