Scientific advances in gene editing hold bold promise to correct genetic mutations at their source and address the underlying causes of disease. The ability to precisely “find and replace” any gene in the genome to cure disease is a revolutionary shift in medicine that offers transformative potential for changing the course of how we treat and cure diseases. For patients such as those who have sickle cell disease, who have been waiting decades for a cure, bringing the promise of gene editing to the bedside cannot come soon enough.
Graphite Bio’s novel approach
Graphite Bio is working to unlock the power of high efficiency, targeted gene correction to cure serious diseases in ways never before possible. The core of the company’s unique approach is its gene editing platform technology, which has a mechanism of action that works similarly to a computer’s “find” and “replace” functions: a state-of-the-art precision CRISPR nuclease “finds” the genetic mutation or damaged portion in the DNA and, utilizing a non-integrating DNA template and the cell’s own innate DNA repair machinery called homology directed repair (HDR), “replaces” the DNA in the target gene. This powerful technology enables broad potential therapeutic approaches: directly correcting a genetic mutation to change a disease-causing gene to a healthy one, replacing a deleted gene or a gene with multiple mutations with a functioning version, or precisely inserting a gene at any location in the genome.
Graphite Bio’s platform allows the gene editing field to move beyond cutting and single base edits by building on CRISPR technology and harnessing the power of HDR, which until now has historically been difficult to achieve at high levels of precision and efficiency.
Tackling sickle cell disease at its genetic roots
In sickle cell disease, a single genetic misspelling is the cause of a disease that affects approximately 100,000 people in the United States and millions of people around the world. The mutation in the beta-globin gene leads to the production of sickle hemoglobin that causes red blood cells to become misshapen, resulting in anemia, blood flow blockages, intense acute and chronic pain, increased risk of stroke, and organ damage. Despite advancements in treatment and care, progressive organ damage continues to cause severe morbidity and early death, highlighting the need for curative therapies.
Genetic editing of hematopoietic stem cells (HSCs), which are the somatic stem cells that give rise to all blood and immune cells for the lifetime of an individual, is a complex process. Editing HSCs requires precise DNA repair technology and extremely efficient and reproducible methodologies to achieve clinical success.
Graphite Bio is using its gene editing technology in hopes of achieving what is considered the gold standard for curing sickle cell disease: direct correction of the genetic mutation in the beta-globin gene to restore normal gene expression to produce normal adult instead of sickle hemoglobin protein, thereby producing healthy red blood cells.
Answering the call of patients
Graphite Bio is working with urgency to translate its powerful gene editing technology into a one-time cure for sickle cell disease. The company is conducting a Phase 1/2 clinical trial of GPH101 (CEDAR), the first investigational therapy to use its highly differentiated gene correction approach. GPH101 is a next-generation gene-edited autologous HSC therapy designed to efficiently and precisely correct the genetic mutation that causes sickle cell disease. Graphite Bio presented details of its CEDAR Trial at the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition.
A world without disease
By fulfilling medicine’s most elusive goal to correct genes anywhere in the genome, the Graphite Bio team aims to make possible the definitive cures that patients, starting with those who have sickle cell disease, have long sought. It’s an aspirational vision that the company’s chief executive officer Dr. Josh Lehrer summed up best.
“I asked a potential new team member to tell me his view of success in the work we do. He told me that success will be measured by the opportunity to walk down the street in the near future and meet a person who used to have sickle cell disease.
“I couldn’t agree more,” says Dr. Lehrer.
To learn how the Graphite Bio is unlocking the potential of gene editing, visit www.graphitebio.com.