Regenerative Medicine and Stem Cells Technologies

Ever since 2012, when researchers first discovered that bacterial immune systems could be hijacked to edit DNA in living creatures, CRISPR has been hailed as a maker of revolutions. This was the year that prediction felt like it was starting to come true. U.S. scientists used the CRISPR gene editing technique to treat a common genetic heart disease in a human embryo. Many more diseases were successfully treated in mice using CRISPR. Hell, a particularly enthusiastic biohacker even spontaneously injected himself with muscle-growth genes while giving a talk at a conference.

But if 2017 was the year that the potential of CRISPR began to come into focus, 2018 may be the year that potential begins to be realized.

Next year, the first human trials of CRISPR-based treatments in the U.S. and Europe are slated to begin.

This month, biotech firm CRISPR Therapeutics became the first to submit a clinical trial application to European regulators. Tests are set to begin next year for its therapy that combines CRISPR gene editing and stem cell therapy to treat the blood disorder beta thalassemia. CEO Samarth Kulkarni told Gizmodo that the company also plans to file an application to conduct a clinical trial using a similar therapy to treat sickle cell disease in the first half of 2018. “In 2018, the first human is going to get dosed with CRISPR in the clinic,” Kulkarni told Gizmodo. “And we’re going to be the first ones to do it.”

Both disorders are genetic, caused by mutations to the genes that produce hemoglobin, a protein essential to ensuring that red blood cells ferry oxygen throughout the body. Without that oxygen, people can suffer from severe anemia, developmental delays, damage to organs, and pulmonary hypertension. The idea is extract stem cells from patients’ bone marrow and correct the faulty genes with CRISPR, a gene-editing technique that allows scientists to cut and paste tiny snippets of genetic code. Then those edited cells would be infused back into the body, where they would multiply, eventually outnumbering the diseased cells. Sickle cell disease and beta thalassemia are good candidates for CRISPR because in many cases, they are caused by a mutation to one single DNA letter.

At Stanford, a different spin on using CRISPR to treat sickle cell disease is also moving toward clinical trials. Matthew Porteus, who heads the research, said that his group expects to file a clinical trial application with the FDA by the end of 2018 and begin trials in 2019. “Our New Year’s resolution for 2018 is to gather the data so we can file a [trial application] by the end of the year, so we can start a clinical trial in 2019,” Porteus told Gizmodo. “We just need to check off all the boxes.”

Chinese scientists, meanwhile, used CRISPR for the first time on a human in 2016, and conducted a second human trial this year, setting off a biomedical duel between the U.S. and China and sparking concerns that the trials were irresponsibly premature. The first U.S. human CRISPR trial was slated to begin this summer at the University of Pennsylvania, after receiving a regulatory stamp of approval to proceed last year. It is unclear what has caused that trial’s delay.

Porteus said that he expects 2018 will bring many more preclinical studies demonstrating how CRISPR might be used to treat different diseases. In 2017, there were several such studies, addressing devastating diseases and conditions such as Huntington’s disease, Lou Gherig’s disease, and an inherited form of hearing loss in mice.

“There is going to be a lot of behind-the-scenes work of turning those into a real clinical protocol,” Porteus said. He also predicted 2018 will see applications for more clinical trials, though most likely ones the involve simply deleting a problematic gene rather than correcting it.

George Church, the famed Harvard geneticist, told Gizmodo that he expects CRISPR will get much more precise in the coming year. He also expects an uptick in research on how to use CRISPR to solve problems that don’t have other good solutions, like eliminating zoonotic diseases such as Lyme disease and malaria by using what’s known as a gene drive to alter the DNA of wild species, or even growing transplantable organs in pigs.

The MIT synthetic biologist Kevin Esvelt said he expects there to be more gene therapy progress using a brand-new CRISPR technique that relies on base editing, or chemically altering a single letter of DNA rather than using CRISPR to actually cut through DNA’s double helix to change it. “The only prediction I’m absolutely confident of making is that 2018 will see CRISPR continue to markedly accelerate research, both by simplifying previously difficult tasks and by making it possible to conduct experiments we could never previously contemplate,” Esvelt said. “Beyond that, there’s no telling.”

Hank Greely, a bioethicist at Stanford, told Gizmodo that he expects to see advancement with CRISPR outside of biomedicine. Among his predictions: “Several groups will come up with completely new and unexpected uses for CRISPR,” he said. And “someone, somewhere will do a gene-drive trial in a controlled but non-laboratory environment.”

Greely also predicts that “CRISPR inventors will win a Nobel prize.” (Though there’s no telling which of CRISPRs inventors—it’s a bitterly disputed claim— that award would go to.)

There are still significant hurdles, though, to reaching a future in which molecular cutting and pasting can act as a one-time cure-all for any genetic disease. For one, treating diseases that require editing DNA while it’s still inside the human body, such as amyotrophic lateral sclerosis, is a lot harder (and riskier) than removing cells, editing them in a lab, and putting them back into the body, as researchers will do in the trials slated to start in the next two years. But addressing many diseases will require what’s known as “in-vivo” treatment. And scientists are still working to figure out the best way to deliver therapies inside the body effectively.

“For ex-vivo treatments, the limit now is just whether we can do the work. I don’t think there are obvious technical challenges. We just need to move into the clinic and test them out,” Porteus said. “For for in-vivo treatments, there is a lot of room for improvement.”

Greely said that while some CRISPR clinical trials will start soon, they won’t wrap up in 2018. Even when science is moving at a breakneck speed, like it is with CRISPR, it still tends to move more slowly than we wish it would.

And we may also realize that the high-tech solution is not always the best option.

Harvard geneticist Church said CRISPR may be due for a “reality check.” For example, he said, families may decide to undergo genetic counseling before having kids to assess their risk of passing on genetic diseases, rather than having children and treating them with “CRISPR therapies likely to be $1 million per dose.”

Whatever is in store for 2018, it’s important to remember that in the realm of science, progress is never a straight line.

Reference: https://gizmodo.com/in-2018-we-will-crispr-human-beings-1821540150