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Why can retroviruses used in stem cell reprogramming create safety concerns?

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Diagram showing the locations of neural stem cells in brain regions such as the hippocampus and ventricles, and hematopoietic stem cells in the bone marrow and blood, with labeled illustrations of the brain, spinal cord, circulatory system, and skeleton. — stem cell Stem cells of neural and hematopoietic origin have tremendous potential in the development of therapies for certain diseases, such as diabetes and Parkinson disease. Neural stem cells occur in the spinal cord and in specific regions of the brain, and hematopoietic stem cells occur in the blood and bone marrow.

In the context of stem cell research, retroviruses are used to transport regulatory genes into the nuclei of adult cells to induce pluripotency. However, this process creates significant safety concerns because the retroviruses incorporate their genetic cargo directly into the host cell's DNA.1

The primary risk is that this integration can lead to malignant transformation, potentially causing diseases such as leukemia in humans. This occurs because retroviruses may insert their genomes into critical sites within the host's cellular genome, such as next to or within a proto-oncogene. This process, known as insertional mutagenesis, can cause a proto-oncogene to become overactive or may inactivate a tumor suppressor gene, both of which can instruct cells to divide uncontrollably and result in cancer.123

Due to these risks, researchers are actively seeking alternative methods, such as the use of plasmids, to introduce reprogramming genes without the tumorigenic potential associated with viral vectors.1