Gene therapy and gene editing have made it possible to cure sickle cell disease and other conditions, and researchers are studying whether gene therapy could also cure HIV. However, current technologies are expensive, risky and require high-tech facilities, making them inaccessible to many of the 38 million people living with HIV today. Dr. Hans-Peter Kiem, director of the Cell & Gene Therapy program at Fred Hutch, hopes to change this.
During a TEDx Seattle talk he gave last November, now available online, Kiem discussed how gene therapy can be used to change the way we treat HIV, cancer and other diseases.
He detailed the experience of the first person cured of HIV, Timothy Ray Brown, who had both HIV and leukemia. His doctors had a radical new idea to cure both, using a bone marrow transplant from a donor whose stem cells contained a mutation on a gene called CCR5.
CCR5 produces a protein that is part of the mechanism HIV uses to enter blood cells. In some cases, when CCR5 is mutated, or broken, HIV can no longer enter the blood cells and no longer infect the body. Some people are born naturally with this mutation, and as Kiem noted, “Timothy’s doctors in Berlin knew about this mutation, and so they looked for and found a marrow donor who was not only a tissue match for Timothy, but who also carried this critical CCR5 mutation.”
The idea was, if the mutation takes hold in the patient, could this cure his HIV?
“And it did, it worked!” Kiem told the audience, leaving Brown cancer- and HIV-free, now for 12 years.
It was this success story that got Kiem thinking about the potential of CRISPR and gene therapies. In his Nov. 23 talk, Kiem described how he hopes to increase the accessibility and application of gene therapies, dubbed “gene therapy in a syringe.”
“Imagine in the not-so-distant-future: With a single injection, a single shot in the arm, we deliver the recipe that will make ordinary blood and immune cells resistant to HIV,” Kiem told the audience. And while it may take some time to perfect, Kiem is confident we are getting closer. Closer to applying gene therapies to not only HIV, but to other conditions.
Through the work he and his colleagues do at Fred Hutch, Kiem hopes to create gene therapies that can cure people “no matter who they are and where they live,” which will allow more people, with different diseases, to benefit from the new technology.
In a paper published in the July 31 issue of Science Translational Medicine, a team of Fred Hutch researchers led by Dr. Hans-Peter Kiem used CRISPR-Cas9 to edit long-lived blood stem cells to reverse the clinical symptoms observed with several blood disorders, including sickle cell disease and beta-thalassemia.
It’s the first time that scientists have specifically edited the genetic makeup of a specialized subset of adult blood stem cells that are the source of all cells in the blood and immune system.
The proof-of-principle study suggests that efficient modification of targeted stem cells could reduce the costs of gene-editing treatments for blood disorders and other diseases while decreasing the risks of unwanted effects that can occur with a less discriminating approach.
“By demonstrating how this select group of cells can be efficiently edited for one type of disease, we hope to use the same approach for conditions such as HIV and some cancers,” said Kiem, director of the Stem Cell and Gene Therapy Program and a member of the Clinical Research Division at Fred Hutch. Kiem also holds the Stephanus Family Endowed Chair for Cell and Gene Therapy.
Drs. Olivier Humbert and Stefan Radtke of the Kiem Lab share first authorship of the paper.
Read more about the study in a Fred Hutch news release.