A group of biotech veterans have debuted today a new company, Homology Medicines, with a bold claim that their underlying science is a better version of the gene editing methods, such as CRISPR-Cas9, that have captured the attention of patients, doctors, and scientists looking to treat desperate diseases.
The claim is, for now, untested, as none of the work has been published. One of the company’s backers says Homology will publish some of its findings soon.
Lexington, MA-based Homology has $43.5 million in Series A financing led by 5AM Ventures and Arch Venture Partners. Its top executives worked together for several years at rare disease drug specialist Shire (NYSE: SHPG).
No surprise, then, that the Homology group—CEO Arthur Tzianabos, chief operating officer Sam Rasty, and chief scientific officer Albert Seymour—aims to go after rare diseases first, possibly blood disorders like sickle cell disease. The startup says it has a technology that might be able to one-up current gene therapy and gene editing approaches.
“We see potential that’s enormous,” says 5AM managing partner and Homology board member Kush Parmar. Homology and its backers believe they can replace faulty, disease-causing genes with healthy ones, without the procedure backfiring and causing safety problems, which is a fear that looms over the development of other genetic surgery methods.
Gene editing is used by researchers to make genetic changes in practically any organism, from mice to pigs to corn to monkeys. There are three main kinds of gene editing; CRISPR-Cas9 is the easiest to use, which in short order since its discovery has made it a mainstay in labs the world over for all kinds of experiments.
But gene editing also has potential to fix a range of terrible genetic diseases. The most advanced form is called zinc finger nucleases from Sangamo Biosciences [NASDAQ: SGMO). Sangamo is conducting a Phase 2 trial to treat HIV infection and has the FDA’s green light to start trials in two other diseases, including hemophilia B. The gene editing technology TALEN will get its first clinical test this year if Pfizer and the French firm Servier move a cell therapy engineered with TALENs into Phase 1 trials for leukemia as planned. As Xconomy noted Friday, medicines based on CRISPR-Cas9 have not yet reached human trials but might next year. Editas Medicine (NASDAQ: EDIT), Intellia Therapeutics, and CRISPR Therapeutics are the three main biotech companies in the field.
Gene therapy, meanwhile—a method of shuttling genetic instructions into the body to provide a long-lasting treatment—has a much longer history than gene editing, dating back three decades. Still, only two gene therapies have been approved in Europe, and none in the U.S. The field has made technical advances but no real impact yet on healthcare.
Homology now says its method of genetic manipulation might have advantages over both gene editing and gene therapy. It says it can effectively recreate a natural biological process known as “homologous recombination,” which cells in humans and other species do to repair DNA damage or, in the case of bacteria, to improve their genetic diversity. In homologous recombination, one chromosome essentially swaps one short DNA sequence for another similar one. (Bacteria can actually swap genes by bumping into one another, which might be considered bacterial sex.)
Homology aims to use homologous recombination to “flip in a gene that’s normal for a gene that’s abnormal,” Tzianabos says.
The procedure will resemble certain types of gene therapy. Homology aims to engineer a piece of “healthy” DNA, pack it into a type of adeno-associated virus, or AAV—a delivery tool commonly used in gene therapy, and now CRISPR technologies as well—and infuse it into the body. In gene therapy, that virus typically gets into a cell and expresses a protein, such as a blood-clotting protein for hemophilia patients, until the cell dies. In Homology’s case, however, the virus carrying the DNA locks on to the cell that needs a genetic fix, enters it, and releases its DNA payload. The healthy DNA then swaps places with the faulty gene inside the patient’s cells. If and when the cells divide, the new cells would carry the fixed gene, not the faulty one. That’s the hope, at least.
The idea of using AAVs to cause homologous recombination isn’t new, however. “People have been working on it for many years,” says Dana Carroll, a genetics expert at the University of Utah. There are pros and cons to the approach, he says. There is no danger of causing … Next Page »