Researchers in the U.S. have started using CRISPR/Cas9 to edit genes in adults with genetic diseases such as sarcoma, myeloma, sickle cell disease, and beta thalassemia.
The CRISPR editing technique involves removing a person’s cells, modifying the DNA, and injecting the cells to potentially target the disease. If the current spate of clinical trials proves successful, they could spur future trials for a variety of other genetic diseases, including Duchenne muscular dystrophy and cystic fibrosis.
Although promising, the technique has several potential limitations. Occasionally, CRISPR/Cas9 targets the wrong genes, resulting in unwanted or unintended edits, known as “off-target” effects. For example, the gene that He Jiankui, PhD, modified DNA in twin embryos using CRISPR in China in 2018 was intended to mitigate HIV risk, but also is associated with a shortened lifespan. Clinical trials of other, less-precise conventional gene therapies that once looked promising have fallen short and led to serious adverse events.
Dr. Jiankui came under investigation for his work, but ongoing trials in the U.S. and China in adults are considered less ethically controversial because those genetic changes won’t be passed on to future generations.
Alan Regenberg, MBe, a bioethicist at the Johns Hopkins Berman Institute of Bioethics, said, “Even if we do make the changes we want to make, there’s still question about whether it will do what we want and not do things we don’t want.”
In trials of CRISPR techniques for cancer and blood disorders, cells are edited outside the patient’s body in lab dishes, then re-infused after a procedure to clear out diseased blood precursor cells. Prior to being reinserted, edited cells undergo quality checks, which may help minimize the risk of unwanted changes.