Genome Editing, Tang Prize Laureates’ Solution to Medical Conundrums

The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race, a book scheduled to come out this March, has Dr. Doudna as the center of its attention. She was jointly awarded the 2016 Tang Prize in Biopharmaceutical Science with Emmanuelle Charpentier and Feng Zhang. Since winning the prize, these three laureates have continued to apply the gene-editing technology CRISPR to the development of medicine, CRISPR-based therapies and cell therapies. The companies each of them co-founded with their partners have “overlapping and distinct target indications”; “all three are targeting haematological disorders”; and many of their key products or therapies are “either in the clinical or pre-clinical stages.” CRISPR Therapeutics, Dr. Charpentier’s company, has also started an “immuo-oncology ” research initiative.[i]   

CRISPR Therapeutics, co-founded by Emmanuelle Charpentier, collaborated with Vertex Pharmaceuticals to develop the gene-editing therapy, CTX001, for the treatment of sickle cell disease and beta thalassemia. This treatment requires a patient’s “hematopoietic stem and progenitor cell” to be “collected from peripheral blood…edited using the CRISPR/Cas9 technology…[and] then be infused back into the patient as a part of a stem cell transplant.”[ii] It has now entered Phase I/II clinical trials. CRISPR Therapeutics “has also initiated early stage clinical trials for its immune-oncology program,” using “allogeneic chimeric antigen receptor T (CAR-T) cells” to zero in on “well-characterised targets in haematological malignancies, such as CD19+ and B cell maturation agent.” The exciting news is that “the development of allogeneic CAR-T cells may circumvent issues with manufacturing and the costs associated with autologous CAR-T cells, which have already demonstrated impressive durable responses in patients with haematological malignancies.”[iii]

Intellia Therapeutic, co-founded by Dr. Jennifer Doudna, takes two approaches to the clinical development of its products, i.e. in vivo and ex vivo. Working with Regeneron, Intellia developed the NTLA-2001 therapy, which introduces “the CRISPR technology into the patient directly via an intravenous route of administration” to tackle “a rare hereditary disorder, transthyretin amyloidosis.” It is now in Phase I clinical trials. On the other hand, the cooperation between Intellia and Novartis focuses on the ex vivo treatments OTQ923/HIX763, which help patients with sickle cell disease by removing their stem cells “for gene-editing” and putting “these repaired cells” back into their bodies.[iv]  

EDIT-101, a medicine developed by Editas Medicine, the company co-founded by Feng Zhang, is designed to treat ocular diseases, especially Leber Congenital Amaurosis (LCA). LCA is caused by “the IVS26 mutation [that] leads to a functional loss in the CEP290 protein,” which accounts for “defects in retinal photoreceptors and severe vision loss.” EDIT-101 has now entered a Phase I/II clinical trial to test whether it “can remove a point mutation in the CEP290 gene.” While Editas and Allergan at first worked together to develop EDIT-101, after AbbVie acquired Allergan, new business strategies and R&D considerations mean that now only Editas is tasked with advancing EDIT-101. In addition, the U.S. Food and Drug Administration has recently allowed Editas to start a Phase I/II clinical trial for its ex vivo medicine, EDIT-301. It is the first CRISPR/Cas12-based therapeutic and is aimed for the treatment of sickle cell disease.[v]

These three companies are all devoted to the improvement of the wellbeing of mankind. Though they have yet to obtain any approval for their products or treatments from the US Food and Drug Administration, there is reason to believe that these three Tang Prize laureates will apply the highest standards in the safety and efficacy of their therapies, foreground the importance of both “basic research” and “clinical applications” that is the core value of the Tang Prize, and emphasize why biopharmaceutical science can be a correct solution to the medical conundrums we face today. All of these efforts will no doubt have lasting, beneficial effect on the health of all humanity.   

[i] All the quotes in this paragraph are taken from “The race for CRISPR-based therapeutics,” https://www.pharmaceutical-technology.com/comment/crispr-based-therapeutics/

[ii] “CRISPR Therapeutics and Vertex Present New Data for Investigational CRISPR/Cas9 Gene-Editing Therapy, CTX001™ at American Society of Hematology Annual Meeting and Exposition, Together with Publication in the New England Journal of Medicine,” http://ir.crisprtx.com/news-releases/news-release-details/crispr-therapeutics-and-vertex-present-new-data-investigational/

[iii] “The race for CRISPR-based therapeutics”

[iv] All the quotes in this paragraph are taken from “The race for CRISPR-based therapeutics”

[v] All the quotes in this paragraph are taken from “First CRISPR therapy dosed,” https://www.nature.com/articles/s41587-020-0493-4

*For the reference of the figure, see “The race for CRISPR-based therapeutics.”