Delaney Van Riper suffers from a mutation in a single gene that leads to stumbling and weakness in her hands and feet. Through the use of the gene-editing technology CRISPR, Van Riper, a student at UC Santa Cruz, hopes to overcome her condition.

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ONVENTIONAL SURGERY can’t help patients such as Delaney Van Riper, a 19-year-old college student with an independent spirit, love of literature and progressive neurological disease. But gene surgery might. In recent weeks, a molecular scalpel began to make test cuts on a troubling mutation in Van Riper’s cells that causes stumbling and weakness in her hands, in hopes of allowing a healthy gene to take over and multiply. While the research is preliminary — her DNA is being changed in the lab, not her body — it’s a step toward fulfilling the therapeutic promise of gene editing, offering a one-time procedure to cure devastating genetic disorders and potentially helping millions of people around the planet. The pioneering research is underway at Dr. Bruce Conklin’s lab as part of the nascent Genome Surgery Initiative, an effort of the UCSF-UC Berkeley Innovative Genomics Institute to see if our genetic blueprint can be fixed as efficiently and effectively as bones, hearts and other parts of the human body. “It’s anatomy that we’re cutting out,” explained Conklin, the UCSF and Gladstone Institutes researcher who co-conceived the Initiative and dreams of making gene surgery widely available to the public. “It’s just very small anatomy.”



Dai Sugano/Bay Area News Group Dr. Bruce Conklin, a researcher at the Gladstone Institutes and UCSF, poses for a photograph with an image of the molecular structure of a disease-causing protein that his team is targeting for removal by genome surgery.

The precise cutting tool, called CRISPR-Cas9, alters the genetic sequences in cells. It isn’t the first gene-editing method. But it is much faster, cheaper, easier and more accurate than earlier versions. “It’s like the Model T — not the first car but the one that changed the world,” according to Hank Greely, director of the Center for Law and the Biosciences at Stanford Law School. Its discovery in 2012 by UC Berkeley’s Jennifer Doudna galvanized the medical community — and now, only five years later, it is moving out of test tubes and toward testing in humans, with clinical trials for various diseases slated to start next year. But it’s no one-trick pony. Different strategies can be enlisted for different disorders. In some surgeries, such as Delaney’s, CRISPR merely cuts out a bad gene. For diseases such as sickle cell, it must cut, correct and replace. There’s no guarantee that CRISPR will cure Delaney of the disease that causes her to stumble when she walks or struggle when she opens a bag of shredded cheese. Things that work perfectly in a test tube often fail in the human body. There are concerns about elevating the risk of cancer or cutting DNA in the wrong place. And CRISPR can’t fix medical problems caused by multiple genes, such as heart disease or diabetes.

Randy Vazquez/ Bay Area News Group Van Riper opens a bag of cheese with a pair of scissors. “I can feel myself telling my body to, like, grip it a certain way or use certain muscles but it doesn’t actually happen,” she said.

But here’s the dream: If research succeeds, then one day — not too far away — doctors could build a common “pipeline” of gene therapies, creating the efficiencies and economies of scale needed to cure the estimated 6,000 to 8,000 single-gene disorders afflicting 350 million people around the world. In support of that vision, Conklin and other innovative Bay Area thinkers are envisioning a path-breaking role for a future Genome Surgery Initiative – a collaboration among UCSF, UC Berkeley and, perhaps, Stanford – that would establish the Bay Area as a center of genetic excellence, spinning off lucrative new innovations. “We’ve always thought about genetic disease as something which is incurable, something that you’re born with,” said Conklin. “We’ve never really thought about it as something that we could actually cut out or repair.” “With this new editing tool,” he said, “we can think about how to do this for the very first time.” ‍

Watch: An introduction to CRISPR