Gene editing's next big targets

• If researchers can perfect gene editing tools and program site-specific editing, the technology could be adapted to treat even more kinds of diseases, as well as create more resilient plants and livestock.

Driving the news: Intellia Therapeutics this week said its CRISPR-based treatment for hereditary angioedema — a rare genetic disorder that causes severe swelling in the body — reduced those attacks by an average of 98% each month in the first 10 patients who received the therapy.

• Dozens of other CRISPR-based therapies are in clinical trials but the treatments can cost millions of dollars and have unintended side effects like inadvertently targeting the wrong genetic sequence.

The latest: Researchers laid out some of the field's most promising avenues and persistent challenges during a virtual event on Wednesday hosted by Genetic Engineering & Biotechnology News.

• Gene integration is one approach being hotly pursued to treat certain diseases in which cells don't make enough of a certain protein. It involves splicing the correct DNA sequence into the genome so more of the protein is produced.
• "It's this last big bottleneck, which a lot of people are working on," said Jonathan Gootenberg, a Harvard Medical School professor and co-founder of Tome Biosciences, a biotech company focused on gene integration technologies.

RNA editing is another frontier that allows larger edits to be made without altering the patient's DNA.

• The goal is to do corrections "at the RNA level without ever having to touch the genome," Gootenberg said. RNA editing's effects could be temporary and reversed, easing some of the safety concerns about altering genetic material that is passed from one generation to the next.
• Several companies and research groups are working on the technology, including Korro Bio, ShapeTX, and Ascidian, which is conducting the first RNA editing clinical trial in the U.S.
• Some suggest the approach — which has the same end goal as DNA editing — could be superior and be used to address a wider range of conditions and diseases.
• But RNA has a short lifespan and degrades quickly, meaning it has its disadvantages as an editing target.

The big picture: Gene editing's biggest successes so far have largely been around inherited disorders.

• "We know for many, many rare diseases, how they work," said Omar Abudayyeh, a Harvard Medical School professor who jointly conducts research with Gootenberg.
• Researchers also have a general concept of how cancer, cardiovascular disease and other conditions work, he said, adding these are a new frontier for gene-editing-based therapies.

But the next unsolved riddle for gene editing — combined with other powerful new tools like single cell analysis — is to answer fundamental questions about aging, Abudayyeh said.

• 'We're very excited about how we can deliver nucleic acids to cells to rejuvenate them, find new rejuvenation pathways, and really make a new potential wave there," he said.

What's next: Beyond humans, gene editing is also being used for precision breeding of cattle, pigs and other livestock.

• About 20% of global livestock production loss is related to animal diseases.
• Gene editing can help improve disease resistance or the ability to withstand variations in temperature, said Alison Van Eenennaam, an animal geneticist and professor at the University of California, Davis.
• Unlike genetically modified organisms that receive DNA from other species, gene editing involves altering the animal's own genome to yield changes that scientists say could arise naturally through selection.

Zoom in: Pigs around the world are affected by a respiratory virus called PRRSV that's persisted globally for more than 30 years, said Elena Rice, chief scientific officer for Genus, an animal genetics company working on introducing resistance to the disease into pigs.

• "Making pigs resistant to that will have a significant impact on industry but also most important the life of pigs," Rice said.
• The company is seeking FDA approval for widespread consumption of its edited pigs.

Yes, but: Some of the standard tools — like prime editing used in human cells — aren't easily adapted to animals, she said.

• "[T]hat's absolutely the next [tool] we need in our toolbox," Rice said.

What to watch: The FDA last year authorized pork from five gene-edited pigs to enter the human food supply in a limited way.

• Cattle edited to have short hair — and the ability to better tolerate high temperatures — have also been deemed "low risk" for market by the FDA.
• In Japan, three fish species edited for more rapid growth are commercially available.

But China leads the way in terms of editing animals, Van Eenennaam said.

• As of last year, there were an estimated 20 gene-edited livestock applications being authorized or reviewed by China's agriculture ministry, according to one analysis.