gene editing


August 2018 Review with Nathan and Laura: The polygenic month

It’s our first show back after the summer break, and nothing has got us all buzzing about genomics again like a polygenic risk score. It even has Laura Hercher talking about the Human Genome Project doing some delivering, god forbid.

CRISPR has had a rough summer. But still . . . it is CRISPR.

Is Burning Man still cool, we were asked last weekend. Don't know. Don't care. We asked back, is 23andMe still cool?

Then we found sort of an answer in an old rag purchased last week down at the end of the street: "They rode into town on the cool train. They've been shoot'n it up out here in the Wild West makin' trouble for the sheriff. But now they've become one of the big corporations who hire their own guards to watch o'er their stage coach. They're makin' woopy with the big guys."

Surely it's talking about 23andMe.

Laura says 23andMe's heyday is past. Nathan says, no, their best is yet to come. And then he immediately gets excited about Neanderthals and Denisovan's having a love child 50,000 years ago.

Non sequitur?

January 2018 Review Show with Nathan and Laura: CRISPR vs The Immune System, Biotech Math, and MinION's Big Test

Some stocks are up on news of big biotech mergers, but others are down on hearing of the latest difficulties of gene therapy. One thing’s for sure—blood diseases are where it’s at.

Speaking of the latest difficulties, we start our January review by going back to that paper out of Stanford about a new obstacle to using CRISPR as a new drug platform. It’s called the human immune system. Major roadblock or small warning light?

“Smart people have been thinking about the wrinkles in CRISPR and Cas9 for a long time. This is one of them, and it’s not going to stop the technology from being used well in people in the long run,” says Nathan.

Neither of our commenters are happy with Luxturna’s pricing of $425,000 per eye. But who is happy with drug pricing these days? How are drug companies supposed to recoup their investment on roughly 2,000 patients?

“We’re gonna have to price these drugs based on the whole platform, but also we’ll have to look at creative things like . . . how successful it is,” says Laura.

Last, but not least, we finish up with the new paper out in Nature showing the sequencing of a reference genome using the MinION handheld nanopore sequencer. Laura says it’s a snooze, but then she comes around.

Sharon Begley of STAT News on the Best of 2017

Sharon Begley joins us for our last show of the year to look back over some of the year’s top stories. She’s the senior science writer at STAT News where she covers genetics, cancer, neuroscience and other fields of biomedical research. Prior to joining STAT, Sharon was the senior health and science correspondent at Reuters, the science columnist at the Wall Street Journal, and the science editor at Newsweek.

If you’re in genomics, you’ve no doubt found yourself reading one of Sharon’s columns. Her range is astonishing, her depth shows years of insider knowledge, and her output prodigious. She managed to write an article on George Church this year that no one had written before. Not easy.

Sharon says her audience has a big industry component and certainly includes people with special interest in the life sciences but it’s also for “ordinary human beings . . . people who go to doctors, who’s friends and loved ones get sick.” That Sharon’s articles can be read by anyone, but are of interest to insiders, makes her a great guest here on the program to see how many of our stories make it out to a larger audience. For instance, in this year when 23andMe’s test rivaled the InstantPot for top seller at Amazon, what does the average person think of genomics in 2017?

In answer, Sharon says that the typical American tends to be a genetic determinist, gullible for any genetic association that comes along--this despite being overwhelmingly religious. Does that mean she proactively takes on the role of pushing back with skepticism?

November 2017 with Nathan and Laura: The Stem Cell Story We’ve All Been Waiting For and a Sea Change for DTC Testing

It didn’t take long to come up with our lead story for November’s month in review show. Looking at the pictures of the boy in Germany playing soccer after successful treatment of his rare skin disease is just the kind of images we had in mind when we first heard of stem cell therapies.

The bulk of our discussion moves on to the incredible bullish drive of direct to consumer testing this year, sparked by a decrease in sequencing costs and a favorable political climate. However, this month FDA commissioner, Scott Gottlieb, showed his cards on the topic of DTC testing as well as LDTs in general, surprising many of us.

Laura says the FDA announcement reflects a “sea change” in that the FDA plans to regulate not “test by test, but the testers.”

Nathan cautions that this policy will encourage companies who already have their FDA clearance based on some sound diagnostic tests to then “down the line put out a test that is much more speculative, based on shakier science.” He says this will privilege the bigger companies who are already established in the space over small innovative companies.

It’s November’s genomic headlines with Nathan and Laura.

September 2017 with Nathan and Laura: Venter Blunder, RNAi Returns, and Monthly Science Moments

To honor Laura's pentametric thirst,

We write the summary today in verse.

 

Was it a quake that had no epicenter,

That silly paper out by J. Craig Venter?

 

And after years of silencing the market

Has RNAi at last knocked out its target?

 

Then Nathan gives to yuppies devil's choice.

Which one libs: gluten dough or GMOs?

 

August 2017 Review with Nathan and Laura: CAR-T Cashes In, Embryos Edited in US, and the Invitae Incident

Back from summer vacation, Nathan and Laura are smoking hot as they look back over some exciting headlines.

The summer boiled over with plenty to talk about, but it was just this week that delivered most of the news for our discussion today. Novartis’ gene therapy based on CAR-T technology was approved Wednesday, making it the first gene therapy to be approved ever in the US. Analysts will be trying to figure out how high high is when it comes to the price tag, but Nathan and Laura explain why this therapy is a big deal for patients.

As for the first gene editing of embryos in the US that happened earlier in August? Nathan says, yes, it’s a first, but the big story is how "strikingly reliable the CRISPR edit is in germline vs the rest of the body."

Finally, we heard a few days ago that genetic testing provider, Invitae (recently featured here on the program) had sent out a large batch of false negative tests. Laura, a genetic counselor, says that in the absence of FDA regulation the system is operating on trust.

“And I want to say,” she adds, “ I trust Invitae. They’re a good lab, and I think they’re handling this well.”

 

The First In-Human Gene Editing Trial in the U.S. - And It’s Not with CRISPR

The challenge for the first ever in-human gene editing trial, according to today’s guest, is with the delivery to the body.

“At the moment, the easiest place to deliver your gene or genome editing is to the liver, using AAV which are viruses that seek out and go to the liver cells," says Sandy Macrae, the CEO of Sangamo Therapeutics.

Sangamo is known for two things: They have pioneered the commercialization of an older gene editing technology called Zinc Fingers. And they have done a lot of work in the area of HIV.

Today, Sangamo is enrolling patients in a new trial which they say will be the first "in-vivo" trial using their Zinc Fingers for patients with hemophilia B, Hunter syndrome, and Hurler syndrome. The former gene editing work with the T cells of HIV patients, Sandy says, was done “ex-vivo”, or outside the body.

So why is Sangamo still using Zinc Fingers in the age of CRISPR? Sandy says that the older technology is much better developed for medical applications and is safer. The company has been able to get their off target effects to below the level of detection.

“When I was doing my postdoc, I would have used CRISPR. It’s better if you’re just wanting an easy experiment that isn’t about making a medicine but just getting a quick answer,” he says.

Because Sangamo has been the sole commercial developer of Zinc Fingers with not a lot of intellectual property dispute, the technology didn’t make the big PR splash that CRISPR has—nor, at the same time, did it generate all the fear.

We finish the interview with a question about what was the result of all Sangamo's work in HIV over the years.

George Church on What Comes After CRISPR

George Church joins us today. He’s the Robert Winthrop Professor of . . . . well, he’s George Church. And he confirms that, yes, a movie called “Woolly" is being made about his lab. In the next breath, he reminds us (and himself?) that less than 1% of his press is about the woolly mammoth.

George was honored this year as one of Time Magazine's "Time 100 List", and we’re curious about what topics of conversation come up when he’s with non-scientists. What does he think of Trump (or what he calls “the new politics”)? Is he tempted to join the wave of scientists running for office?

“In China, about 80% of their top government officials have a degree in science or engineering, while in the United States it's closer to 1%,” he deadpans.

We cover some scientific ground today as well. George says CRISPR has been overhyped as the step between Zinc Fingers/Talens and the next gene editing tool. So what is the next CRISPR? And what ever came of his 3-D sequencing?

Enjoy.

Is CRISPR Controversy Science or Spin? June 2017 Review with Nathan and Laura

It’s the end of the month--and the half year mark--so we open up today's monthly discussion with Nathan and Laura to include some of the headlines we’ve missed this year.

Last month a paper was published warning about the off target effects when using CRISPR. Laura and Nathan agree the kerfuffle which exploded into this month was more about Wall Street than adding anything new to science.

Remember the technology we used before CRISPR? Sangamo Biosciences launched the first ever “in vivo” (in human) trial for gene editing using Zinc Finger technology.

Also last month, the FDA approved a drug based on the genetic makeup of a tumor and not its location in the body. Nathan says, “Nyeh . . . And? Doctors have been doing it off label for years.” But Laura thinks it's more that just a symbolic gesture.

She also picked for her paper of the month this new study out by Robert Green’s group asking whether the benefits outweigh the risks for whole genome sequencing in healthy individuals.

"It’s preliminary, but it’s not PR. This is one of the really important questions for genomics in our time," says Laura.

Nathan highlights a paper propounding a new model for biology, the omnigenic model. Find out what that is in another fun and informative look back on the genomics headlines with Nathan Pearson and Laura Hercher.

Over $1 Billion Invested this Past Year: Synthetic Biology in 2017 with John Cumbers

What does it take to make it in synthetic biology in 2017?

Working as a bio engineer at NASA, John Cumbers founded SynBioBeta, the primary “activity hub” for the synthetic biology community. SynBioBeta will be putting on their sixth conference this year in San Francisco, along with conferences in London and Singapore. The young industry has seen a flourish of startups working on new genome engineering tools and a dizzying array of applications that include synthetic animal meat and synthetic human skin. Last month John partnered with Data Collective to launch a new seed stage fund for this space.

John is not only interested in startups. Currently writing a book with the working title, “What’s Your Bio Strategy?”, he is provoking existing companies to consider using biology as technology.

“The book is designed to be something we could take into [Apple CEO] Tim Cook’s office, and ask him what’s your bio strategy. And he says, 'I don’t have a bio strategy.' So you put the book on his desk and say give me a call if we can help you to develop one.”

When we first talked with John, he was heading up a program at NASA to develop building materials for use on Mars. Five years later, is John's number one goal in life still to settle the solar system?



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