US bid to grow human organs for transplant inside pigs BBC News

[Goritoes]

Pigs DNA is very similar to Humans, it does some good for medical research but also increase the risk of transferring the diseases' in future.

 

[Beast]

She’s hellbent on solving the organ shortage with ‘designer pigs.’ Just don’t keep her waiting
By Sharon Begley
April 6, 2017

Luhan Yang, cofounder and chief scientific officer of eGenesis, in its lab in Cambridge, Mass.KAYANA SZYMCZAK FOR STAT

CAMBRIDGE, Mass. — Where other people see bacon, biologist Luhan Yang sees lifesaving organs — hundreds and thousands of them, pig livers and pig kidneys and diabetes-curing pancreases, and possibly hearts and lungs, all growing inside droves of pampered swine.

More established scientists than Yang have dreamed of creating animal organs that are suitable for transplantation into people waiting for a human donor. But until recently, experts said it would take decades to genetically alter pig organs to make them work safely in people. Most xeno dreamers gave up.

Giving up is not in Yang’s lexicon. Urgency is. In her native China, she told STAT, 2 million people need organ transplants, “and people are dying before they get one.”

The intensely driven 31-year-old has a few things going for her that other would-be pioneers did not. As a Harvard graduate student, Yang was a lead author of a breakthrough 2013 study on the genome-editing technology CRISPR-Cas9. And in 2015, she cofounded the biotech company eGenesis with her mentor, legendary Harvard bioengineer George Church, with whom she’s also worked on trying to resurrect the Ice Age wooly mammoth through genetic legerdemain. From eGenesis’s tiny headquarters in Kendall Square, she intends to use CRISPR to accomplish what the world’s largest drug companies failed to despite investing billions of dollars: create “designer pigs” whose organs can be transplanted into people.

“Luhan is a remarkable person,” Church said, “and a force of nature.”

She better be. Daunting hurdles stand between where biology is now and where it needs to be to make transplantable pig organs. The old problems of infection and rejection of another species’ organs seem almost quaint compared to those confronting eGenesis.

There’s the challenge of CRISPR’ing an unprecedented number of genes without compromising the viability of the designer pigs and without introducing aberrant edits. And of optimizing mammalian cloning, which is how the company creates the pigs. And of persuading investors and doctors that xenotransplantation is safe, effective, ethical — and lucrative.

Yang, eGenesis’s chief scientific officer, has already made enormous strides, scientific and financial. In 2015, she and colleagues in Church’s lab used CRISPR to eliminate from pig cells 62 genes so potentially dangerous their very existence nixed previous efforts to turn pigs into organ donors. Last month, eGenesis announced that it had raised $38 million from investors. The next hurdle: get the surrogate-mother sows that are pregnant with genetically altered embryos to give birth to healthy piglets.

“Her work has the potential to change the face of transplantation and to save countless lives,” said Dr. James Markmann, chief of transplant surgery at Massachusetts General Hospital.

Yang is not only confident of success; she also sees eGenesis’s xeno work as a sort of trial run for even bolder goals. In 2016, she helped conceive Genome Project-write, whose aims include assembling a synthetic human genome from off-the-shelf parts and — because, really, as long as you’re making a human genome, why not? — doing it better than nature.

By starting from scratch, she wonders, “could we make the human genome cancer-resistant? … Or make it virus-resistant? … There is a great opportunity that xeno can tell us what would happen in humans after dramatic genome engineering.”

But if eGenesis is to succeed in making designer pigs, let alone paving the way for new and improved humans, Yang will need to fix the miscarriage problem.


A Petri dish with human embryonic kidney cells at the eGenesis lab, where scientists are taking the first steps toward creating genetically altered “designer pigs.”KAYANA SZYMCZAK FOR STAT

A ton of genetic handiwork
On a frigid March morning, Yang is holding her monthly meeting with Church and the company’s half-dozen employees, getting updates on the designer-pig pipeline and lighting a fire under her team. The big conference table in the windowless, unadorned basement room is strewn with 8.5-ounce cans of “Wild Jujube Drink” and snacks that Yang brought back from her Lunar New Year visit to China, where she spent five days with her parents and visited eGenesis’s pig colony.

The “highlight of the month,” biologist Marc Guell tells Yang, is that surrogate mother pigs didn’t reinfect fetuses with “PERVs.” That’s crucial, because the memorably named infectious agents, short for porcine endogenous retroviruses, could cause tumors, leukemia, and neuronal degeneration if transplanted into patients. To make xenotransplantation succeed, PERVs have to go.

PERV genes are interwoven into the genome of pig cells, so eGenesis scientists start their work with CRISPR-Cas9, which has made editing organisms’ genomes so simple high-schoolers can do it. It takes far more expertise, however, to remove dozens of PERV genes at once, as eGenesis does in pig fibroblasts, which are connective-tissue cells.

eGenesis ships batches of these cells to China, where each de-PERV’ed pig cell is fused with a pig ovum whose own DNA has been removed. The ova, which now contain only the PERV-free genome, start dividing and multiplying, beginning the journey to becoming pig fetuses. (This adult-cell-plus-ova technique was used to clone Dolly the sheep.) The embryos are implanted into surrogate mothers and, if all goes well, born 114 days later. (Yang won’t say how many sows are or have been pregnant.) Unfortunately, all has not gone well.

The anti-PERV work is only the start of the changes eGenesis is making to pig genomes. Its scientists are also slipping into the pig ova up to 12 human genes “to make the pig organs more human-like,” Yang said in an interview. One gene, she said, would shield its organs from attack by the human immune system; another would revamp its coagulation system to reduce the risk of clots.

That’s a ton of genetic handiwork for one little pig to handle, and early signs are it might be too much.

One batch of embryos all died, Yang said, possibly because their chromosomes had gotten scrambled by either the genetic changes or the lab manipulations. Another batch had “a lot of miscarriage,” she said.

There are other concerns, scientists noted at the March meeting. Sometimes PERVs are found in the embryos before they’re implanted into surrogate mothers. The problem, Yang says as she leaps to the front of the conference room, is that removing the DNA-containing nuclei from pig ova isn’t always complete; occasionally some of an ovum’s own PERV-infested genes remain behind, so the embryo created from it also has PERVs, genetic analyses showed.

Yang grills her team. How prevalent is this? May I see the genetic profile again? What can we do quickly to correct the protocol? A gene that was inserted to protect other genes “is the problem,” she says with finality. “Maybe we should pause this one and look for other solutions. It’s better to figure out where the problem comes from, then we don’t have the problem anymore.”


A research station at eGenesis, which is using CRISPR to rid pig genomes of viruses and make the animals’ organs safe for human transplant.KAYANA SZYMCZAK FOR STAT

‘We’re short of time’
A clue to how Yang’s mind works is that she counts. Ask her about the ethical issues around xenotransplantation and she will immediately tell you there are three, then elaborate on them. Ask her what characteristics make up the “entrepreneurial spirit” and she will say there are four, then reel them off. Colleagues say she has an uncanny knack for working backward from an ultimate goal and breaking it into a manageable sequence of steps.

She darts down corridors, speaks quickly, hates waiting, and expects others to move at her speed. Some colleagues call her impatient. Biologist Dong Niu, who worked in the Church lab and is now at eGenesis, accompanied Yang on a recent blitz of apartment hunting. Yang set such a breakneck pace, Niu said, “I couldn’t even watch.”

“Luhan is a remarkable person and a force of nature.”
GEORGE CHURCH

When eGenesis was packing up a previous office, waiting for the movers irritated Yang so much that she plopped her computer and other belongings into a child’s Radio Flyer wagon and took off.

Even on vacation, Yang operates on fast-forward, jet skiing while visiting places like Hawaii. Closer to home, she unwinds by having friends and coworkers over for dinner and karaoke, making sure to order enough so her guests can take home leftovers.

She pushes colleagues to accomplish tasks — analyzing DNA edits, checking the viability of cells — now, if not sooner, and when she asks a coworker to explain a scientific detail, she says, “We’re short of time; just get to the point.”

Yet colleagues sing her praises, saying she motivates them and brings “extraordinary passion” and a “laser focus” to her work. “Whenever you have a question, she has an answer, almost before you get it out,” said Niu.

Coworkers also mention her kindnesses, like the sweltering summer day when the tiny Yang passed a discarded air conditioner on a Cambridge street and, on foot, hauled it to the eGenesis office 30 minutes away. She left it on the desk of a colleague whose apartment had no AC.

Yang was born and grew up in a small town in a mountainous region of southwest China. Her parents were “ordinary working class people,” she told STAT, her father a government employee and her mother an accountant.

Her hometown is named for the Chinese Buddha who represents wisdom. “Because of that we have a lot of temples in the mountain,” she said. “And because of that I was very fascinated by nature when I was young. I think that had an influence on how I decided my career path.”

In 2004, as a high school senior, she was chosen for China’s four-person team in the 15th International Biology Olympiad, held in Australia. The global competition consisted of a written test on biological theory and a practical test of lab techniques. Yang was one of 16 contestants to win a gold medal, coming in 13th.

Source

She's hellbent on solving the organ shortage with 'designer pigs.' Just don't keep her waiting

Biologist Luhan Yang and eGenesis are using CRISPR genome-editing to create "designer pigs" whose organs can be transplanted into humans.

www.statnews.com

I think she already left Cambridge and started her own company.

Luhan Yang

Luhan Yang wants to work toward a world where no one dies waiting for a vital organ transplant. Yang holds degrees from Peking University and Harvard University, where she worked with legendary geneticist George Church. She went on to cofound xenotransplantation firm eGenesis with Church in...

fortune.com

Definitely real stuff than faked Therano Holmes.

 

[Nan Yang]

I think she already left Cambridge and started her own company.

Luhan Yang

Luhan Yang wants to work toward a world where no one dies waiting for a vital organ transplant. Yang holds degrees from Peking University and Harvard University, where she worked with legendary geneticist George Church. She went on to cofound xenotransplantation firm eGenesis with Church in...

fortune.com

Definitely real stuff than faked Therano Holmes.

More about Yang Luhan contribution to this field.

 

[Polestar 2]

The genetic modify heart transplant to human is her work. Congratulation.

In historic first, surgeons transplant a genetically modified pig heart into a dying patient

Two and a half months after an NYU team dubiously claimed to have performed the first ever pig-to-human organ transplant, a team at the University of Maryland Medical Center ...

endpts.com

Scientists are divided on the exact number of edits needed to prevent rejection. Revivicor has been competing with a couple academic labs and eGenesis, the venture capital favorite, to make xenotransplantation a reality. eGenesis, founded by genetic engineer Luhan Yang and backed with over $260 million from private investors, makes an even higher number of edits — they’ve never said quite how many — as they try to eliminate PERV entirely.

 

[大汉奸柳传志]

how disgusting. I'd rather die

 

[-blitzkrieg-]

new fitna in market

 

[Hamartia Antidote]

The genetic modify heart transplant to human is her work. Congratulation.

Revivicor has been competing with a couple academic labs and eGenesis, the venture capital favorite, to make xenotransplantation a reality. eGenesis, founded by genetic engineer Luhan Yang and backed with over $260 million from private investors, makes an even higher number of edits — they’ve never said quite how many — as they try to eliminate PERV entirely.

Wow you completely misread that. Why so desperate to take credit that you see things incorrectly??

It says Revivicor (the company that provided the pig organs) is competing with eGenesis (Luhan Yang's company). It was obviously not her work at all.