CRISPR technology to cure sickle cell disease at UIC

January 20, 2021

University of Illinois Chicago is one of the U.S. sites participating in clinical trials to cure severe red blood congenital diseases such as sickle cell anemia or Thalassemia by safely modifying the DNA of patients' blood cells.

The first cases treated with this approach were recently published in an article co-authored by Dr. Damiano Rondelli, the Michael Reese Professor of Hematology at the UIC College of Medicine. The article reports two patients have been cured of beta thalassemia and sickle cell disease after their own genes were edited with CRISPR-Cas9 technology. The two researchers who invented this technology received the Nobel Prize in Chemistry in 2020.

In the paper published in the New England Journal of Medicine, CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia, researchers reported gene editing modified the DNA of stem cells by deleting the gene BCL11A, the gene responsible for suppressing fetal hemoglobin production. By doing so, stem cells start producing fetal hemoglobin so that patients with congenital hemoglobin defects (beta thalassemia or sickle cell disease) make enough fetal hemoglobin to overcome the effect of the defective hemoglobin that causes their disease.

The advantage of this approach is that it uses the patient's cells with no need for a donor. Also, the gene manipulation does not use a viral vector as with other gene therapy studies but is done with electroporation (quick production of pores into the cells with high voltage) which is known to have low risk of off-target gene activation, according to Rondelli.

Sickle cell disease is an inherited defect of the hemoglobin that causes the red blood cells to become crescent-shaped. These cells can lyse and obstruct small blood vessels, depriving the body's tissues of oxygen. The disease can cause extreme pain and damage the lungs, heart, kidneys and liver. Beta thalassemia is a blood disorder that reduces the production of hemoglobin -- the iron-containing protein in red blood cells that carries oxygen to cells throughout the body. In people with beta thalassemia, low levels of hemoglobin lead to a lack of oxygen in many parts of the body.

The first two patients to receive the treatment have had successful results and continue to be monitored. Rondelli is on the steering committee for an international clinical trial, with UIC being the only site in Chicago. Although the trial is at an early stage and the first patients will be followed for some time before expanding the numbers worldwide, UIC will be among the few sites ready for this treatment.

"It is a great privilege for UIC to be part of this international study and I hope that in the future we will have our own patients undergo this procedure," Rondelli said.

"UIC and UI Health is an ideal place for any cellular therapy in sickle cell disease because of our experience and success in stem cell transplantation in these patients. In fact, over 75% of sickle cell patients can be cured with a transplant, and we have already done over 50 cases," he said.

While a full-match donor is still the first line of treatment, finding a compatible stem cell donor is challenging. For this reason, many centers including UI health have developed strategies to successfully utilize donors who are only 50% compatible, called haploidentical donors. However, according to Rondelli, in about 30% to 50% of the patients, there are still multiple barriers that can limit the possibility of a donor-derived transplant, such as a family donor availability, or the presence of antibodies in the patient caused by many prior red cell transfusions, that would reject the donor stem cells.

"This gene-editing procedure has the potential to overcome all of these. Cells of the same patient can be manipulated and can be transplanted without the risk of rejection or to cause immune reactions from the donor (graft-versus-host disease)," said Rondelli. "For the almost 900 patients with SC coming to our hospital, this should be great news."

Patients who in the future will participate in the trial will have cells sent to the CRISPR manufacturing site where the cells undergo genetic editing. Patients then receive chemotherapy prior to the edited stem cells being re-inserted into their bloodstream.

Researchers hope this treatment can be a game-changer for world health. Sickle cell disease and beta thalassemia and other congenital blood disorders are major diseases in the world. Rondelli said 5 million people only in Nigeria suffer from sickle cell disease, and many others in Africa. Also, currently, 30% of transplants being performed in India, which has 1.3 billion people, are to treat severe beta thalassemia, he added.

"The hope is that this treatment will be accessible and affordable in many low-middle-income countries the Middle East, Africa, and India, and have an important impact in the lives of many people in these areas," said Rondelli.
-end-
The CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia research paper was authored by Haydar Frangoul and Jennifer Domm of the Sarah Cannon Center for Blood Cancer at the Children's Hospital at TriStar Centennial, Nashville; Akshay Sharma of St. Jude Children's Research Hospital, Memphis; David Altshuler, Brenda K Eustace, Julie Lekstrom-Himes and Angela Yen of Vertex Pharmaceuticals; Martin Steinberg of Boston University School of Medicine; Yi-Shan Chen, Tony Ho, Andrew Kernytsky and Sandeep Soni of CRISPR Therapeutics, Cambridge, Massachusetts; M. Domenica Cappellini of University of Milan; Franco Locatelli of Ospedale Pediatrico Bambino Gesù Rome, Sapienza, University of Rome; Juergen Foell and Selim Corbacioglu of University of Regensburg, Regensburg, Germany; Rupert Handgretinge of Children's University Hospital, University of Tübingen, Tübingen, Germany; Josu de la Fuente of Imperial College Healthcare NHS Trust, St. Mary's Hospital, London; Stephan Grup of Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia; Antonis Kattamis of University of Athens, Athens; Amanda Li of BC Children's Hospital, University of British Columbia, Vancouver; Donna Wall of Hospital for Sick Children-University of Toronto; Markus Mapara of Columbia University, New York; Sujit Sheth of Joan and Sanford I. Weill Medical College of Cornell University, New York; Mariane de Montalembert of Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris; and Damiano Rondelli, University of Illinois Chicago.

Funded by CRISPR Therapeutics and Vertex Pharmaceuticals; ClinicalTrials.gov numbers, NCT03655678 for CLIMB THAL-111 and NCT03745287 for CLIMB SCD-121.

University of Illinois at Chicago

Related Science Articles from Brightsurf:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.

Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.

Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.

Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.

World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.

PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.

Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.

Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.

Read More: Science News and Science Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.