Harvard geneticist George Church, who cofounded Editas, says the CRISPR/CAS gene therapy technology’s ability to change single base pairs enables fundamentally new ways of thinking about gene therapy. Many inherited diseases, including cystic fibrosis and sickle-cell anemia, are caused by single base pair changes to the DNA sequence of genes; the precise CRISPR/Cas technology could correct these mutations in patients.
Editas Medicine is new startup, backed with $43 million in venture investments, aims to develop treatments that could cure inherited diseases with a one-time fix based on a new method of genome editing. The method offers great precision in changing the DNA sequence of a genome and can potentially treat diseases that other forms of gene therapy cannot.
CRISPR (clustered, regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) and TALENs (transcription activator-like effector nucleases) comprise novel gene editing methods that overcome the challenges associated with previous technologies. Early published research on CRISPR/Cas9, coupled with a growing body of work on TALENs, suggests the potential to pursue therapeutic indications that have previously been intractable to traditional gene therapy, gene knock-down or other genome modification techniques. The CRISPR/Cas9 system, the most recent and exciting approach to emerge, acts by a mechanism in which the Cas9 protein binds to specific RNA molecules. The RNA molecules then guide the Cas9 complex to the exact location in the genome that requires repair. CRISPR/Cas9 uniquely enables highly efficient knock-out, knock-down or selective editing of defective genes in the context of their natural promoters, unlocking the ability to treat the root cause of a broad range of diseases.
“Editas is poised to bring genome editing to fruition as a new therapeutic modality, essentially debugging errors in the human software that cause disease,” said Alexis Borisy, director, Editas Medicine and partner, Third Rock Ventures. “Our CRISPR/Cas9 technology is favorably differentiated due to its ability to pursue almost the entire genome, allowing broad therapeutic application and the targeting of defective genes in a highly specific, selective and efficient manner.
Traditional methods of gene therapy are limited. Generally, the treatments involve adding a functional copy of a gene to a patient’s cells. The healthy copy can either incorporate itself into the patient’s genome or it can remain a distinct entity, depending on the particular design of the treatment. This means the original dysfunctional copy of the gene remains. In cases where the dysfunctional gene produces nothing or a harmless, broken protein, this added gene method works. However, if the dysfunctional gene produces a dangerous version of a protein, or if other DNA mutations cause a gene to be overproduced to the point of toxicity, adding a healthy copy will not treat the resulting disease.
CRISPR/Cas could address these sorts of diseases, says Church. Take Huntington’s disease, an inherited neurodegenerative disorder caused by a toxic protein made by a dysfunctional gene. Traditional methods of gene therapy cannot address this disease, but CRISPR/Cas has the potential to correct the faulty DNA sequence.
Another advantage of the gene-editing potential of CRISPR/Cas technology is that the corrected gene remains in its normal chromosome location, which preserves the way the cell normally turns a gene on or off. With CRISPR/Cas, “all the natural program controls, the natural responses are all in place,” says Borisy.
Editas will need to address a number of issues with the technology to turn it into a medicine. For one, the CRISPR/Cas system can make unwanted cuts in the genome if its guide RNA nearly matches other DNA regions outside the gene that researchers want to treat. Another area to explore is how to best deliver the molecular tools into a patient’s cells. But the founders are confident that the expertise in the company, which includes many of the pioneers of CRISPR/Cas, will lead to ways to address these issues.
The company’s founders won’t talk specifically about the diseases they will try to address, but say they will focus on grievous diseases that are currently not treatable.