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First human trials of the genome-editing technology CRISPR/Cas9 may be moving forward

Last month, the NIH Recombinant DNA Advisory Committee approved the first human trials of the genome-editing technology CRISPR/Cas9 for creating genetically-altered immune cells to attack three types of cancer. The next step is to seek approval from the US Food and Drug Administration (FDA) and the medical centers where the study would be conducted. If approved, the study, funded by the Parker Institute for Cancer Immunotherapy, will enroll patients with multiple myeloma, melanoma, and sarcoma.

What is CRISPR? What is Cas9? CRISPR stands for Clustered Regularly-Interspaced Short Palindromic Repeats. CRISPRs are part of the bacterial immune system, and they defend against invading viruses. They consist of repeating sequences of genetic code interrupted by “spacer” sequences – remnants of genetic code from past invaders. The system helps the cell detect and destroy invaders when they return. Cas9 is one of the enzymes produced by the CRISPR system that binds to the DNA and snips it, shutting the targeted gene off.

Scientists have known for decades that genetic mutations cause disease. Many say that if we could go into the genes and change these mutations to the normal sequence, this technology could potentially cure disease. Other gene-editing techniques exist, but they are slow, imprecise, and very difficult.

For years scientists sought to understand how they could adapt CRISPR’s mechanism for use in humans. In the last few years, scientists have developed a deeper understanding of how CRISPR and Cas9 interact. Using modified versions of Cas9, researchers can activate gene expression instead of cutting the DNA. CRISPR/Cas9 has the potential to target and modify mutations in the three-billion-letter sequence of the human genome to treat genetic disease. Some scientists have compared it to correcting a typo in a gene – deleting the wrong letter and replacing it with the right one.

What would the study involve? A team at the University of Pennsylvania proposed the trial that the NIH committee approved. If approved, University of Pennsylvania, the MD Anderson Cancer Center in Houston, and the University of California at San Francisco would conduct the study with approximately 15 patients. The researchers will remove T cells (a type of white blood cell) from the patients and edit them using CRISPR before injecting the cells back into the patient. The first CRISPR edit will insert a protein engineered to detect cancer cells and instruct the T cells to target them, and the second will remove a protein that could interfere with this process. The third edit will remove the gene that identifies the T cells as immune cells to prevent the cancer cells from disabling the T cells. While more approvals are still needed, the trial could start as early as next year.

Analysis: Potential applications for CRISPR range from curing different diseases, to growing organs that could be used in transplants, to possibly preventing genetic diseases in embryos.

While many in the scientific community are citing CRISPR/Cas9 as one of the biggest breakthroughs in modern medicine, many researchers are proceeding with caution. One concern is that CRISPR could snip other genes and potentially create new cancer genes or trigger existing ones. The University of Pennsylvania-led team plans to carefully measure the growth rate of the engineered T cells and test for genomic abnormalities. Another concern is that the technique could activate the body’s immune response. For these reasons, leaders in the field are cautioning that the scientific community must proceed carefully to ensure the benefits outweigh the risks from potential misuse and unforeseen consequences.

Rachel Reeves, “CRISPR cancer therapy trial gets go-ahead in US,” BioNews UK, June 27, 2016; Broad Institute, “What is CRISPR?” 2016.

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Author bio

Doug leads Deloitte Consulting LLP’s Life Sciences and Health Care practice. With 24 years of experience, he works closely with multiple top health care organizations on major clinical and enterprise transformation efforts and on large-scale technology implementation projects. Doug has extensive experience in comprehensive quality and patient safety transformations, turnaround and performance improvement in academic medical centers as well as organization/workflow redesign and technology enablement. He has served as the lead on a number of enterprise transformation initiatives with some of Deloitte’s most largest and most complex clients.