A technique for editing genes could lead to new ways to treat some diseases.

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CRISPR technique for editing genes may eventually be used to single out and destroy genes that cause disease

Editas, already developing CRISPR-based therapies, recently received a large investment to expand its research

CNN  — 

A popular new gene therapy technology could help treat cataracts, liver disease, muscular dystrophy and other conditions. But the technology, dubbed the “Genesis Engine” by some, has not been tested in people yet, so no one knows whether it would be a safe and effective treatment option.

The potentially revolutionary genome-editing tool known as CRISPR is based on something that bacteria do naturally. About a decade ago, scientists realized that bacterial cells possess a defense system that recognizes and chops up the DNA of invading viruses. They dubbed it CRISPR – an acronym for clustered, regularly interspaced, short palindromic repeats – because of the mechanics of how the system’s components worked.

The primitive defense system rocketed to prime time in the last couple of years after a study suggested that it could be adapted to work in other types of cells, including human, and possibly single out and destroy genes that are responsible for disease.

Editas Medicine, a biotech company in Cambridge, Massachusetts, is already using the gene therapy technology to develop treatments for cancers of the blood and a rare eye disorder, said CEO Katrine Bosley.

A large investment of $120 million to Editas could help the technology do more. The firm called bng0, which is backed by Bill Gates, made the investment in Editas. The new money will allow the company to explore what other conditions might be treated with CRISPR, as well as develop more ways that CRISPR can tweak the genome, Bosley said.

“The investors … took a very deep look at the science at Editas and at our plans,” she said. “I think it really shows their tremendous belief in the future of genome editing and how we hope to translate this science into medicine,” she added.

By now, CRISPR is being used by many researchers for scores of applications – not just to develop treatments for disease, but to answer basic questions about what genes do. Researchers wipe out a gene using CRISPR and see what effect it has on the cell.

All it takes is delivering two molecules into cells: a small piece of RNA, which is a close cousin to DNA, and an enzyme that makes a cut in DNA. The RNA is designed to recognize and bind to the gene of interest – and hopefully only that gene. The RNA also ushers the enzyme to that gene, which cleaves the gene and consequently turns off its activity in the cell.

One of the factors that will determine how realistic it will be to move CRISPR from the lab – and the cells in Petri dishes and mice where it has been mostly studied – into patients is how accessible the cells are in the human body, Bosley said.

The diseases that scientists at Editas are currently working on, an eye disorder and blood cancer, involve cells that are relatively easy to access. For the first, the components of CRISPR would be injected into the retina in order to delete a gene that is responsible for a form of Leber congenital amaurosis, a rare eye disorder that impairs vision from infancy.

Although this project is relatively far along in development, the company is still figuring out which molecules to use in the CRISPR cocktail, so it is too soon to say when it could be tested in clinical trials in people, Bosley said.

As for Editas’ work on blood cancer, the strategy would be to remove cells from the body, use CRISPR to tweak the genome of immune cells to program them to recognize cancers, and return those cells to the body. This work, which Editas is doing in collaboration with Juno Therapeutics Inc. in Seattle, is early in its development, Bosley said.

In theory at least, there are no cells in the body that the CRISPR system could not get to, said Kamel Khalili, professor and chair of the neuroscience department at Temple University School of Medicine. Nanoparticles and viruses (the kind that do not cause disease) could be used as vectors to deliver CRISPR to the brain and other hard-to-reach places, he said.

Khalili and his colleagues have shown that CRISPR can target copies of the HIV virus that lie in the genome, effectively suppressing infection, at least in cells in Petri dishes. It is unclear how long it could take to bring this kind of therapy to people, but Khalili is hopeful that trials will start in less than 10 years. “The important thing is that we have a technology that we never had before,” said Khalili, who is not affiliated with Editas.

Just like all the gene therapy attempts before it, CRISPR faces a number of challenges. “We talk about all the good things of the … system and a couple of things need to get close attention,” Khalili said. In addition to the challenge of delivering CRISPR to the right part of the body, a big question “is whether or not the system is going to impact the host genome. It’s scissors that you are sending in the nucleus of cells with sharp edges that can cause problems,” he said.

The potential of CRISPR to chop up unintended regions of the genome, known as off-target effects, is one of the main concerns about turning this technology into treatment. “It has to be addressed before it enters clinical trials,” said Dr. Bence Gyorgy, a research fellow at Massachusetts General Hospital. However, as researchers learn more about CRISPR, they are getting better at making it specific for the gene of interest, he added.

Gyorgy, along with his collaborators Casey Maguire and Xandra Breakefield, is working with lab mice in an effort to develop CRISPR-based approaches to treat Alzheimer’s disease and to correct a genetic form of deafness. Right now the technology is better suited for destroying “bad” versions of genes that cause disease, but scientists hope in the future it will also be able to replace those versions with normal, healthy copies of the gene, Gyorgy said. He and his team are not affiliated with Editas.

While there aren’t any studies of CRISPR-based therapies in people yet, several clinical studies using another gene therapy technology, called zinc finger nucleases, are underway to treat people with HIV. Although this technology might be inherently less prone to off-target effects than CRISPR, it is more expensive and cumbersome to develop, Khalili said.

Although researchers at Editas and elsewhere are putting their hopes on CRISPR, Bosley said that other gene editing therapies could also be helpful. “If they all work, all the better,” she said.