Gene drive is both a promising and disturbing technology. It allows us to engineer a stretch of DNA that, once inserted in a specific location in an organism’s genome, will convert other versions of the gene so that they also carry the insert. Once started in a population, gene drive will convert the entire population within a relatively short number of generations.
That’s promising, in that it opens the door to editing mosquitos to cause sterility to spread through a population, eliminating the spread of diseases and a fair bit of itching. But it’s also a genie that, once out of the bottle, appears to be impossible to put back—and hence is disturbing. But so far, there has been a small consolation: it has only been shown to work in insects.
Now, a large research team at the University of California, San Diego, has managed to get it working in mice. Sort of. It turns out that the efficiency is much lower. While the gene drive DNA is inherited at rates well above normal Mendel-style inheritance, it’s nowhere near as effective as in insects, and it’s not clear we know how to fix it.
Chinese authorities have declared the work of He Jiankui, who shocked the scientific community by claiming he successfully created the world’s first gene-edited babies, an illegal decision in pursuit of “personal fame and gain.” Investigators have completed preliminary steps in a probe that began in November following He’s claims and say they will “seriously” punish the researcher for violations of the law, China’s official news agency Xinhua reported on Monday.
He, who taught at Shenzhen’s Southern University of Science and Technology, had led a team to research the gene-editing technique CRISPR since mid-2016 in attempts to treat cancers and other diseases. The incident drew significant attention to the professor’s own biotech startups that are backed by local and overseas investors.
The official probe shows that He fabricated ethics approvals which he used to recruit eight couples to participate in clinical procedures between March 2017 and November 2018. The attempt led to two pregnancies, including one that resulted in the birth of twins and the other embryo yet to be born. Five couples failed to achieve fertilization and one pair dropped out of the experiment.
He’s project has sparked a wave of criticism among scientists across the world. CRISPR is still dangerously unethical at this point for it may cause serious genetic damage. Some researchers have proposed a moratorium on CRISPR until more guidelines become clear while others call for developing safer and more ethical methods to propel the technology forward. Many countries, including the United States and China, prohibit gene-editing of human embryos for reproductive purposes.
The up to $818 million deal between Locus Biosciences and Janssen Pharmaceuticals (a division of Johnson & Johnson) that was announced yesterday points toward a new path for CRISPR gene editing technologies and (potentially) the whole field of microbiome-targeted therapies.
Based in Research Triangle Park, N.C., Locus is commercializing research initially developed by scientists at North Carolina State University that focused on Cas3 proteins, which devour DNA Pac-Man-style, rather than edit it like the more well-known Cas9-based CRISPR technologies being used by companies like Caribou Biosciences, Editas Medicine, Synthego, Intellia Therapeutics, CRISPR Therapeutics and Beam Therapeutics.
While the Cas9 CRISPR technologies can edit targeted DNA — either deleting specific genetic material or replacing it with different genetic code — Cas3 simply removes DNA strains. “Its purpose is the destruction of invading DNA,” says Locus chief executive, Paul Garofolo.
The exclusive deal between Janssen Pharmaceuticals and Locus gives Janssen the exclusive license to develop, manufacture and commercialize CRISPR-Cas3-enhanced products targeting bacterial pathogens for the potential treatment of respiratory and other organ infections.
Under the terms of the deal, Locus is getting $20 million in upfront payments and could receive up to $798 million in potential future development and commercial milestone payments and any royalties on potential product sales.
A former executive at Valiant Pharmaceuticals and Paytheon, Garofolo was first introduced to the technology that would form the core of Locus as an executive in residence at North Carolina State University. It was there that he met Dr. Chase Beisel and Rodolphe Barrangou, whose research into Cas3 proteins would eventually be productized by Locus.
The company spun out of NC State in 2015 and raised its first cash from the North Carolina Biotech Center a year later.
Locus is already commercializing a version of its technology with bacteriophages designed to target e coli bacteria to treat urinary tract infections. The company is on target to begin its first clinical trials in the third quarter of the year.
The focus on bacterial infection and removing harmful bacteria while ensuring that the rest of a patient’s microbiome is intact is a huge step forward for treating diseases that scientists believe could be linked to bacterial health in a body, according to Garofolo.
“Most microbiome companies are about adding probiotics to your body,” says Garofolo, representing a thesis that introducing “good” bacteria to the body can offset any harmful pathogens that have infected it.
“Things you’re exposed to are creating the groundwork for an infection or disease, or exacerbating an existing disease,” says Garofolo. And while he believes that the microbiome is the next big field for scientific discovery, the approach of adding probiotics to a system seems less targeted and effective to him.
Already, Garofolo has managed to convince investors of his approach. In addition to the initial outside investment from the North Carolina Biotech Center, Locus has attracted $25 million in financing from investors, including Artis Ventures and the venture capital arm of the Chinese internet giant, Tencent.
Meanwhile, investors have spent millions backing alternative approaches to improving human health through the manipulation of the microbiome.
Companies like Second Genome, Viome and Ubiome are all using approaches that identify bacteria in the human body and try to regulate the production of that bacteria through diet and probiotic pills. It’s an approach that allows these companies to skirt the more stringent requirements the Food and Drug Administration has put in place for drugs.
That doesn’t mean that extensive amounts of research haven’t gone into the development of these probiotics. Seed, a Los Angeles-based startup that launched last year, has recruited as its chief scientist George Reid, the leading scientist on microbial health and the microbiome.
Founded by Raja Dhir, a graduate from the University of Southern California and a leading researcher on microbiotics in his own right, and Ara Katz, the former chief marketing officer of BeachMint and an MIT Media Lab fellow, Seed focuses on developing probiotic treatments using well-established research.
“Foundational to our approach is that it’s not which microbes are present in your gut… It’s based on looking at what specific microbes can do to a healthy individual to improve that status of health independent of what is already present,” Dhir said in an interview around the company’s launch last June. “It’s a little bit less exciting from a tech perspective, but it’s hardcore grounded in basic science… The question is, does this have changes and effects in validated bio-makers in a controlled and placebo setting?”
Dhir said that a basic understanding of how different bacteria can influence health is necessary before getting into the benefits of personalization.
“These things can dance between drugs and nutrition,” Dhir said. “Probacteria are an additional lever that people should pull… like diet and exercise and cessation of smoking… In every correspondence we always have been and need to be clear that this should never be seen as a replacement of therapies.”
By contrast, the tools that Locus is developing are very much therapies with potentially far-reaching implications for illnesses, from irritable bowel syndrome to gastrointestinal cancers and even neurological disorders.
“The science [around the microbiome] is early, but it is very well-known that a potentially deadly pathogen should be removed from your body,” Garofolo said.
As more details regarding the first gene-edited humans are released, things continue to look worse. The researcher who claimed the advance, He Jiankui, has now given a public talk that includes many details on the changes made at the DNA level. The details make a couple of things clear: we don’t know whether the editing will protect the two children from HIV infections, and we can’t tell whether any areas of the genome have been damaged by the procedure.
All of that raises even further questions as to whether He followed ethical guidelines when performing the work and getting consent from the parents. And, more generally, nobody is sure why He chose to ignore a strong consensus that the procedure wasn’t yet ready for use in humans. In response to the outcry, the Chinese government has shut down all further research by He, even as it was revealed that a third gene-edited baby may be on the way.
While the US already has rules in place that are intended to keep research like He’s from happening, a legal scholar Ars spoke with suggested there may be a loophole that could allow something similar here. In light of that, it’s important to understand the big picture He has potentially altered. What exactly happened in China and why does it concern so many in the scientific community?
On Sunday, news reports indicated that the first gene-edited human babies had been born in China. As of right now, the information on what, exactly, has been accomplished is confusing. The scientist behind the announcement has made a variety of claims but has not submitted his data to the community in order for his claims to be verified. But even in its current state, the announcement has set off a firestorm of criticism within the scientific and ethics communities. Most scientists feel that the technology isn’t ready for use in humans and that there are better ways to deal with the problem the work was addressing: HIV infection.
He is expected to present more details of his work on Wednesday, but it’s clear that he used biotechnology called CRISPR to perform the gene editing. CRISPR is a system that evolved in bacteria to protect them from viruses by allowing them to recognize and cut viral DNA. By changing part of the CRISPR system, it’s possible to direct it to cut an arbitrary DNA sequence. That can include sequences within the human genome.
In a dramatic development for CRISPR research, a Chinese scientist from a university in Shenzhen claims he has succeeded in helping create the world’s first genetically-edited babies. Dr. Jiankui He told the Associated Press that twin girls were born earlier this month after he edited their embryos using CRISPR technology to remove the CCR5 gene, which plays a critical role in enabling many forms of the HIV virus to infect cells.
The AP’s interview comes after the MIT Technology Review reported earlier today that He’s team at the Southern University of Science and Technology wants to use CRISPR technology to eliminate the CCR5 gene and create children with resistance to HIV. The news also comes the day before the Second International Summit on Human Genome Editing is set to begin in Hong Kong.
According to the Technology Review, the summit’s organizers were apparently not notified of He’s plans for the study, though the AP reports that He informed them today. (It is important to note that there is still no independent confirmation of He’s claim and that it has not been published in a peer-reviewed journal.)
During his interview with the AP, He, who studied at Rice and Stanford before returning to China, said he felt “a strong responsibility that it’s not just to make a first, but also make it an example” and that “society will decide what to do next.”
According to documents linked by the Technology Review, the study was approved by the Medical Ethics Committee of Shenzhen HOME Women’s and Children’s Hospital. The summary on the Chinese Clinical Trial Registry also says the study’s execution time is between March 7, 2017 to March 7, 2019, and that was seeking married couples living in China who meet its health and age requirements and are willing to undergo IVF therapy. The research team wrote that their goal is to “obtain healthy children to avoid HIV providing new insights for the future elimination of major genetic diseases in early human embryos.”
A table attached to the trial’s listing on the Chinese Clinical Trial Registry said genetic tests have already been carried out on fetuses of 12, 19, and 24 weeks of gestational age, though it is unclear if those pregnancies included the one that resulted in the birth of the twin girls, whose parents wish to remain anonymous.
“I believe this is going to help the families and their children,” He told the AP, adding that if the study causes harm, “I would feel the same pain as they do and it’s going to be my own responsibility.”
Chinese scientists at Sun Yat-sen University in Guangzhou first edited the genes of a human embryo using CRISPR technology (the acronym stands for Clustered Regularly Interspaced Short Palindromic Repeats), which enables the removal of specific genes by acting as a very precise pair of “genetic scissors,” in 2015. Though other scientists, including in the United States, have conducted similar research since then, the Southern University of Science and Technology’s study is considered especially radical because many scientists are wary of the ethical implications of CRISPR, which they fear may be used to perpetuate eugenics or create “designer babies” if carried out on embryos meant to be carried to term.
As in the United States and many European countries, using a genetically-engineered embryo in a pregnancy is already prohibited in China, though the Technology Review points out that this guideline, which was issued to IVF clinics in 2003, may not carry the weight of the law.
In 2015, shortly after the Sun Yat-sen University experiment (which was conducted on embryos that were unviable because of chromosomal effects) became known, a meeting called by several groups, including the National Academy of Sciences of the United States, the Institute of Medicine, the Chinese Academy of Sciences and the Royal Society of London, called for a moratorium on making inheritable changes to the human genome.
In addition to ethical concerns, Fyodor Urnov, a gene-editing scientist and associate director of the Altius Institute for Biomedical Sciences, a nonprofit in Seattle, told the technology Review that He’s study is cause for “regret and concern” because it may also overshadow progress in gene-editing research currently being carried out on adults with HIV.
TechCrunch has contacted He for comment at his university email.
Paul Dabrowski, the chief executive officer of Synthego, which provides genetically engineered cells to scientists and researchers, worries about a future where access to the genetic technologies that will reshape the world are only available to the few who can afford them.
To hear him tell it, that’s why Dabrowski began working on Synthego in the first place — to democratize access to the new technologies that will give scientists, researchers, and consumers new ways to rewrite the code that has defined human existence.
“People talk about access to the tools, but the question is access to the therapies,” Dabrowski said. “We’re talking about the basis of what does it mean to be human not right now, but in the next 100 years.”
Now, the company has a fresh $110 million in cash from new investors at Founders Fund and the company’s previous backers — 8VC and Menlo Ventures — to try and drive costs down.
“This new funding allows us to expand our reach and build out of our full stack platform capabilities at a perfect time,” said Dabrowski, co-founder and CEO, Synthego, in a statement. “Biological medicines are on the cusp of a revolution with the coming curative cell and gene therapies, and we are proud to support this industry.”
While Dabrowski said the financing will be used for further research and development — and bringing new services to market — in the near term the funding will be used to expand two main areas of interest for the company. One is the creation of CRISPR kits that can create different genetic lines based on the requests from researchers and scientists, and the other is creating materials that are “clinical-grade”, which means that they can be used in clinical trials on animal (and potentially human) subjects.
“In general the demand for these products is quite high. Building capacity and building out the informatics models for the predictability on the CRISPR research side.
In all, the Redwood City, Calif.-based company has raised $166 million in funding to develop its technology that makes research and development using the gene editing tool known as CRISPR more economical and faster for researchers. Synthego claims that by offering researchers one-click access to engineered cells with guaranteed edits in their desired target, the company can slash the time it takes to conduct experiments by months, enabling predictable and rapid outcomes in cell and gene therapy research and development.
As we’d written previously, Synthego launched its first CRISPR offerings to the market earlier this year.
There are two basic functions that people use CRISPR for, said Dabrowski. The first is to remove a gene or function and the second is adding a function to genetic material.
Both of those processes involve three (very complicated) steps. First scientists have to identify the gene that they want to target and then understand what genetic material within that gene they want to target for removal. Then a research team would need to identify and procure the reagents and components they need to edit a gene. Finally, the team would need to figure out whether the edit was made successfully and watch for results when the edited genetic material is cultivated.
Synthego’s first set of products were designed to simplify the process for identifying and designing genetic material for experimentation. This next set of tools are supposed to help scientists by providing them with the material they want to observe or experiment with.
“Our vision is a future where cell and gene therapies are ultimately as accessible as vaccines, so that everyone can benefit from next-generation cures,” said Dabrowski in a statement. “Synthego will continue to innovate to help researchers redefine the boundaries of transformative medicines.”
At least 2 million people in the U.S. become infected with so-called “super bugs” and at least 23,000 people die as a direct result of these infections each year, according to the Centers for Disease Control (CDC). Now, HP’s Biohacker technology is working with the CDC on a pilot program to “print” and test antibiotics in an effort to catch these antimicrobial resistant strains from spreading faster.
The HP D300e Digital Dispenser BioPrinter technology works by using the same set up as a regular ink printer, but instead dispenses any combination of drugs in volumes from picoliters to microliters to be used for research purposes.
Part of the reason these bugs spread so rapidly often comes down to mis-use of antibiotics, leading the bacteria to develop a resistance to the drugs available. The CDC hopes to give hospital providers access to the technology nationwide to cut down on the problem.
“Once a drug is approved for use, the countdown begins until resistance emerges,” Jean Patel, PhD, D (ABMM), Science Team Lead, Antibiotic Resistance Coordination and Strategy Unit at CDC said in a statement. “To save lives and protect people, it is vital to make technology accessible to hospital labs nationwide. We hope this pilot will help ensure our newest drugs last longer and put gold-standard lab results in healthcare providers’ hands faster.”
The 3D bioprinting sector has been experiencing rapid growth over the last few years and will continue on pace through the next decade, mainly due to R&D, according to market researchers. Innovation in the space includes printing of organs and human tissue and drug research and development.
Further, this potentially valuable antibiotic resistance research could help patient care teams stem a grim future where we experience a regression in health and life spans due to no longer having the ability to treat currently curable diseases.
The HP BioPrinter is currently used by labs and pharmaceutical companies such as Gilead, which tests for drugs used against the Ebola virus. It is also being used in various CRISPR applications. The CDC will use these printers in four regional areas spread throughout the U.S. within the Antibiotic Resistance (AR) Lab Network to develop antimicrobial susceptibility test methods for new drugs, according to HP.