Our Science: Overview
Targeted Integration: The Next Revolution of Gene Editing
Graphite Bio stands apart in the field of gene editing through its approach of using proprietary CRISPR technology to achieve high efficiency, targeted gene integration that addresses the underlying causes of diseases. Our targeted approach is designed to precisely replace defective genes at their native chromosomal location, allowing for the production of normal gene expression within the inserted cells, potentially avoiding the safety issues associated with first-generation gene editing approaches, gene knock-out technologies and single base gene editing. This novel approach holds broad potential in applications well beyond genetic diseases – including cancer, autoimmune and neurodegenerative diseases – by engineering disease-fighting functions into a variety of cell types.
Highly differentiated, targeted gene integration platform
The goal for Graphite Bio’s targeted gene integration platform is to repair genetic defects at their source by combining exquisite targeting of the gene replacement machinery to genomic locations with DNA mutations, along with a DNA donor template that harnesses a cell’s own innate DNA repair mechanism called homology directed repair (HDR). The Graphite Bio technology platform is designed to work similarly to a computer’s “find” and “replace” functions: CRISPR nuclease precisely “finds” the mutated DNA in the defective gene or targeted location and the HDR process, utilizing the Graphite Bio DNA template, then “replaces” in the new DNA to correct the defect or insert a new gene.
Unleashing the full potential of stem cells to cure disease
Initially, Graphite Bio is focused on correcting genetic defects and replacing genes within 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. The self-renewing HSCs are corrected ex vivo and reinfused into patients. Graphite Bio’s platform is designed to enable these HSCs to differentiate into the appropriate blood and immune cells with restored function – providing the potential for long-term disease remissions and even cures.
Genetic repair of HSCs for use as therapeutics is a complex process that requires, in addition to exquisitely precise DNA repair technology, extremely efficient and reproducible methodologies for patient HSC isolation, engineering and manufacturing to the scale and quality required for clinical use. In addition to optimized DNA “find” and “replace” repair functions, Graphite Bio’s platform is designed to provide key solutions for the challenging process of editing HSCs – which have been historically difficult to achieve high rates of HDR – and ensuring efficient incorporation of repaired genes into the genome. Using our platform, we have been able to increase HDR up to 70% efficiency in preclinical models, harnessing our vast scientific expertise in the optimization of this process.