World's First CRISPR Clinical Trial

Author:  Young Joon Kim

Institution:  Columbia University

Oncologist Lu You’s research group at Sichuan University injected a patient with CRISPR modified cells on November 15, marking the first time CRISPR gene-editing has been tested in a human. The team delivered modified cells into a patient suffering from aggressive lung cancer as part of their clinical trial at the West China Hospital in Chengdu. The study stands as a key milestone in the CRISPR revolution, which began in 2013 with the discovery of CRISPR’s genome editing potential.

CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeat, are short, repeated sequences of palindromic DNA that are found interspersed throughout bacterial genome. In between these CRISPR sequences are “spacer” sequences, which are portions of viral DNA that have been replicated and stored from prior viral invasions. When a virus attacks bacteria that contain matching “spacer” sequences, a RNA transcript, called CRISPR RNA, of the corresponding “spacer” sequence is constructed from bacterial “memory.” Finally, a delivery protein lines up the CRISPR RNA and the foreign viral DNA and either cuts up or modifies the latter, forming an immune response.

Laboratories and hospitals can use this immune machinery to edit DNA of any species. One can construct CRISPR RNA that corresponds to a gene of interest then let the efficient and accurate CRISPR delivery system identify the gene and either modify or disable it. The potential for CRISPR-based treatment in treating genetic diseases, including various cancers, has become apparent in the past few years of the CRISPR revolution.

Gene-editing therapies, other than those that rely on CRISPR, have recently been applied to human patients with astonishing success. In November 2015, Immunologist Waseem Qasim of Great Ormond Street Hospital for Children NHS Trust in London successfully treated a one-year-old girl with leukemia by injecting her with T-cells that were extracted from a healthy donor and edited with another DNA-cutting protein called a TALEN. CRISPR’s main advantage over existing gene therapies stems from its relative affordability, efficiency, and ease-of-use, which makes it an attractive option for physicians around the world.

Using CRISPR, Dr. Lu You’s team removed immune cells from the patient’s blood and disabled a gene that codes for the protein PD-1, which normally suppresses a cell’s immune response. Cancers such as leukemia have been known to take advantage of immune system inhibition by PD-1. Then, the researchers re-injected the edited PD-1 disabled cells into the patient, hoping that the uninhibited immune cells would overwhelm the malignant cells.

Although Dr. Lu You’s study marks the first time CRISPR has been utilized to treat human patients, various other CRISPR clinical trials will begin in the coming months and years. The National Institute of Health (NIH) approved the United States’ first CRISPR clinical trial at the University of Pennsylvania under the leadership of Dr. Edward Stadtmauer. The study revolves around a similar strategy to that of Dr. Lu You’s project: modifying and injecting healthy T-cells  into patients with leukemia. Likewise, similar trials have been recently approved for bladder cancer, prostate cancer, and renal carcinoma at Peking University.

Aware of the enormous therapeutic potential CRISPR harbors for patients with cancers and other genetic diseases, clinics in the US and China are racing to bring CRISPR to the forefront of human medicine. Dr. Carl June, who is involved in the aforementioned study at the University of Pennsylvania, states: “I think this is going to trigger ‘Sputnik 2.0,’ a biomedical duel on progress between China and the United States, which is important since competition usually improves the end product.” Although CRISPR-based treatments have made enormous progress since their inception only a few years ago, it seems more investigation is necessary in order to fully harness the power of CRISPR .